A novel murine model of infective endocarditis mimics human pathophysiology

A novel murine model of infective endocarditis mimics human pathophysiology | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A novel murine model of infective endocarditis mimics human pathophysiology Benedikt Bartsch, Ansgar Ackerschott, Muntadher Al Zaidi, Raul Nicolas Jamin, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4313097/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Apr, 2025 Read the published version in PLOS ONE → Version 1 posted You are reading this latest preprint version Abstract Incidence of Infective endocarditis (IE) and its mortality rate despite optimal medical therapy remain high. Early diagnosis and treatment initiation are challenging because the involved immunological processes are poorly understood due to a lack of suitable in vivo models and their difference to human pathophysiology. Objectives : To establish a novel reproducible murine IE model, based on wire injury (WI) induced endothelial damage. Methods : IE was established by inducing endothelial damage via wire injury followed by bacterial challenge with S. aureus using 10 4–6 colony-forming units (CFU). Cross-sections of valvular leaflets were prepared for scanning electron microscopy (SEM) and immunofluorescence microscopy to visualize valvular invasion of macrophages, neutrophils, and S. aureus. Bacterial cultivation was carried out from blood and valve samples. Results : Wire injury induced endothelial damage was observed in all mice after wire-injury in SEM imaging. We reliably induced IE using 10 5 (85%) and 10 6 (91%) CFU S. aureus after wire injury. We found significant neutrophilia in the blood and increased valvular immune cell and bacterial accumulations in IE mice. Conclusion : Our model allows for reliable IE induction and analysis of bacterial vegetation and immune cell infiltration in vivo and ex vivo . Valvular immune cell infiltration was similar to human pathophysiology. Cardiac & Cardiovascular Systems Infective Endocarditis Staphylococcus aureus aortic stenosis Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Infective endocarditis (IE) is defined as a bacterial infection of the heart, most commonly affecting the heart valves (van den Brink, Swaans et al. 2017). Its incidence is increasing in developed countries, and it has high mortality rates of up to 30% (Tackling and Lala 2019 , Delgado, Ajmone Marsan et al. 2023). Despite optimal medical therapy and a trend towards early surgical intervention, mortality rates remain high (Cahill, Baddour et al. 2017). Major complications include septic stroke or acute heart failure (Cahill, Baddour et al. 2017, Delgado, Ajmone Marsan et al. 2023).Patients initially present with only mild symptoms and no direct IE-specific surrogates; echocardiography, CT or PET-CT scans are often inconclusive, hindering early diagnosis and treatment (Delgado, Ajmone Marsan et al. 2023). Risk factors for IE include cardiac procedures such as valve replacement or pre-existing innate or degenerative valvular disease (Vahanian, Beyersdorf et al. 2022, Delgado, Ajmone Marsan et al. 2023). The most common bacteria causing IE in developed countries is Staphylococcus aureus (S. aureus), and its incidence is increasing (van den Brink, Swaans et al. 2017). The aortic valve is the most commonly affected valve in IE due to the prevalence of aortic valve stenosis (AS) in the elderly with up to 2% (Goody, Hosen et al. 2020, Luehr, Bauernschmitt et al. 2020). While its progression is often slow and asymptotic, severe AS has a mortality rate in the range of 50% if untreated (Otto and Prendergast 2014 ). Our understanding of the mechanisms that cause IE and inflammatory responses is still limited. Bacteriemia is considered a precursor of both native and prosthetic IE (Werdan, Dietz et al. 2014, Iung 2019 , Liesenborghs, Meyers et al. 2020). Healthy heart valves have a natural barrier to bacterial adhesion and infiltration consisting of an intact endothelial layer, making patients with previous valvular pathology such as stenosis or rheumatic fever susceptible to bacterial metastasis due to a potential lack of endothelial protection (Werdan, Dietz et al. 2014). While pre-existing valvular pathologies are common among IE patients, only few patients with pre-existing valvular pathologies develop IE, demonstrating a need to better understand the early pathophysiology of IE induction (Bussani, De-Giorgio et al. 2019). Endothelial damage exposes the underlying tissue of collagen matrix and interstitial cells to the bloodstream, resulting in fibrin and von Willebrand factor (vWF) adhesion and platelet activation, leading to microthrombotic lesions (Liesenborghs, Meyers et al. 2019). During episodes of bacteremia, these lesions act as gateways for bacterial infiltration. S. aureus expresses abundant adhesive surface proteins, making it an ideal pathogen to infiltrate valves with prior endothelial damage (Ahmed, Meghji et al. 2001). After valve infiltration, S. aureus promotes further platelet activation with its surface proteins (McDevitt, Francois et al. 1995). Platelet activation is facilitated by soluble fibrin within damaged valves, which creates a protective shield that impedes immune cell infiltration and serves as an ideal environment for bacterial adhesion (Fitzgerald, Foster and Cox 2006, Liesenborghs, Meyers et al. 2019). While further direct immune cell interaction with the bacteria is impeded by the fibrin-platelet coat, monocytes, macrophages and neutrophils were shown to infiltrate IE valves (Kaiser, Joppich et al. 2022). IE patients often show an increase of neutrophils in peripheral blood counts which normalizes after treatment initation. To further evade the immune response, S. aureus can infiltrate both, endothelial cells and fibroblasts using FnBPs (Werdan, Dietz et al. 2014). Intracellularly, it can release toxins and exoenzymes, including α-hemolysin, which can induce cell death and further aggravate valve damage (Hocke, Temmesfeld-Wollbrueck et al. 2006). Alternatively, once intracellular, S. aureus can switch between slow and fast metabolism depending on environmental changes, resulting in chronic and therapy-resistant infections (Proctor, Von Eiff et al. 2006). To date, existing murine models of IE either lacked an adequate immune response, making quantification or localization analysis difficult, or exhibited signs of fulminant septic shock, including valvular abscess formation (Gibson, Kreuser et al. 2007, Ring, Hoerr et al. 2014, Liesenborghs, Meyers et al. 2019). To date, most models rely on either a single i.v. injection (between 10 5–7 CFU) of bacteria or permanent placement of a 32-G catheter across the aortic valve, ignoring the most common clinical setting in which IE develops within pre-existing endothelial damage of the heart valves (e.g., AS). We have recently introduced a novel murine model of AS, which allows us to reliably induce AS in mice (Niepmann, Steffen et al. 2019). In this study, we aim to establish a murine model of IE that mimics the most common clinical setting: endothelial damage followed by bacteremia via i.v. S. aureus injection. Methods Mice The mice used in this study were male and female C57BL/6-J (wild-type), aged between 10 to 12 weeks, and obtained from Janvier Labs, France. The animals were provided with ad libitum access to drinking water and food. The room in which the mice were kept maintained a temperature of 22°C and followed a 12-hour light cycle. The study was conducted in accordance with the guidelines set by the Animal Ethics Committee of the North Rhine-Westphalian State Agency for Nature, Environment, and Consumer Protection in Germany (AZ 81-02.04.2020.A174). Echocardiography For the assessment of valvular function, mice were sedated with 1.5% isoflurane under strict surveillance of respiratory rate, electrocardiogram, and body temperature. Aortic valve peak velocity, aortic regurgitation, and bacterial valve vegetations were measured in the suprasternal view. Other standard echocardiographic parameters such as left ventricular ejection fraction, fractional shortening, and ventricular volumes were measured in the parasternal long-axis views. Regurgitation jets of the aortic valve were defined as follows: in immediate proximity to the aortic valve: mild; if jets reached the length of the left ventricular outflow tract: moderate; and if jets reached beyond the outflow tract: severe. Wire injury The wire injury procedure was conducted following a recently published protocol from our facility (Niepmann et al., 2019 ). In brief, mice were anesthetized using an intraperitoneal injection of 150 mg/kg Ketamine and 16 mg/kg Xylazine. The right carotid artery was surgically accessed, and a straight guidewire with a shortened and soldered tip (Abbott HI-TORQUE 0.014) was used. Blood flow was halted with the application of two ligatures. Echocardiography was employed to confirm the correct placement of the inserted wire into the left ventricle through the trans-aortic valve. To induce endothelial damage, the wire was moved back and forth across the valve 50 times and rotated 100 times. During the procedure, echocardiography was immediately performed to ensure that no aortic regurgitation occurred. Subsequently, the wire was removed, and the artery was ligated. Bacterial challenge and cultivation The methicillin-susceptible S. aureus strain SA-LT 68/03C12Y7, isolated from human samples, was preserved at -80°C in 20% glycerol. To create the bacterial challenge suspension, S. aureus was cultured with LB media for 8 hours at 37°C, using a slow, pivoting motion. Subsequently, the bacteria were suspended in sterile 0.9% NaCl to reach a concentration of 10 4–6 CFU/100 µl. Prior to the experiment, the appropriate bacterial volumes were confirmed by inoculating 10 µl of bacteria on 5% blood agar plates (BD Biosciences). The bacterial challenge was carried out either 1 day or 3 days after the wire injury by intravenously injecting 0.1 ml of the bacterial suspension. After injection S. aureus blood cultures were collected from the animals and cultivated on 5% blood agar plates. Histological preparation Mice were euthanized via cervical dislocation 1d, 3d, or 7d after the bacterial challenge. Hearts were extracted using sterile instruments and were flushed with sterile 0.9% saline solution. Hearts where then either purified using Precellys® or made available to immunofluorescence. Under a light microscope magnification of 10x, the hearts were opened by making a sagittal incision along the left ventricular outflow tract. Any remaining blood clots were eliminated using sterile 0.9% saline solution. CD68 and CD45 staining was used to visualize immune cell and macrophage infiltration of the aortic valve as described in Niepmann et al 2019 . For Ly6G staining, aortic valve sections were fixed in Acetone for 30 min and blocked with 10% normal goat serum (NGS). The primary antibody was diluted 1:200 (anti Ly6G, rat 1A8 anti mouse, BD Biosciences, USA) and incubated overnight. The secondary antibody was diluted 1:500 (Cy3 AffiniPure Donkey anti Rat IgG, Jackson ImmunoResearch Laboratories Inc) and incubated for 90 minutes. For S. aureus staining, aortic valve sections were fixed in 0.1% Saponin for 30 min and blocked with 10% NGS. The primary antibody was diluted 1:200 (Anti-S. aureus IgG rabbit, ab20920, Abcam, UK) and incubated overnight. The secondary antibody was diluted 1:1000 (AlexaFluor 647, goat anti rabbit, ThermoFisher Scientific, USA) and incubated for 1h. NucBlue™ (DAPI) (ThermoFisher Scientific, USA) was used for counterstaining of the nuclei. Flow cytometry For quantification of immune responses, 50 µl of whole blood was collected. Red blood cells were filtered, and Fc receptors were blocked (Fc-Block, Pharmingen). After washing, cells were stained using anti-Ly6G (BioLegend), anti-B220 (BioLegend), anti-CD11b (BioLegend), anti-CD3 (eBioscience), CD45 (BioLegend) and anti NK1.1 (BioLegend). For flow cytometry we used FACSCanto II (BD Bioscience, Franklin Lakes, USA) and analyzed the data with FlowJo (Tree Star, Ashland, USA). Scanning electron microscopy (SEM) Samples underwent fixation through transcardiac perfusion with 6% glutaraldehyde in phosphate buffer. For preparation in scanning electron microscopy, the samples were rinsed in phosphate buffer and subsequently post-fixed in 2% osmium tetroxide in phosphate buffer for 2 hours at room temperature. Dehydration was achieved using a graded ethanol series, followed by a transition to acetone. Afterward, this intermediate step was eliminated using a critical point dryer, and a coating of 8 nm of platinum was applied using a sputter coater, prior to visualization using a scanning electron microscope (Jeol 7500F). Statistical analysis The data presented is shown as mean ± SEM. Appropriate assumptions of data (e.g. normal distribution or similar variation between experimental groups) were examined before statistical tests were conducted. The number of experiments and the number of mice per group are provided in the figure legends. Student’s t-tests were used whenever two groups were compared, and one-way or two-way analyses of variance followed by Tukey’s test for multiple comparisons. The analysis was performed with Prism 8 (GraphPad Software, Inc. La Jolla, CA). The results are provided as mean unless noted otherwise; p < 0.05 was considered statistically significant. Results Wire injury + bacterial challenge mice showed increased bacteremia and valvular infiltration levels of S. aureus Since bacteremia is considered a necessary precursor in IE development, we first tested bacterial challenge via intravenous injection in wild-type C57BL/6-J mice using 10 4 , 10 5 and 10 6 CFU S. aureus for spontaneous development of IE (Fig. 1 a). Blood cultures and cultures from valvular samples revealed dose dependent blood bacterial titers and valvular bacterial colonies (Fig. 1 b + c). The overall success rate of IE induction confirmed with valvular cultures was 22% (10 4 CFU), 27% (10 5 CFU) and 67% (10 6 CFU) (Fig. 1 d). Mortality in mice with bacterial challenge (BC) only was 4.5%. Mice receiving 10 6 CFU bacterial challenge suffered severe morbidity including peripheral abscess formation and clinical signs of sepsis including weight loss, reduced mobility and decreased fur grooming. The immunological response following bacterial challenge using concentrations of 10 5 and 10 6 CFU was verified by increased neutrophil counts. Both relative and absolute neutrophil counts were higher when bacterial challenge was performed using 10 6 CFU (p 0.001) (Online Resource 1). Because a singular bacterial challenge at concentrations below the sepsis threshold was unreliable in inducing endocarditis, we extended our experimental protocol to include a wire injury of the aortic valve before bacterial challenge to create endothelial damage, which we hypothesized to increase the likelihood of endocarditis (Fig. 1 e). Bacterial challenge was performed either 24h or 72h after wire injury. Blood cultures and cultures from valvular samples revealed dose dependent blood bacterial titers and valvular bacterial colonies (Fig. 1 g + h). While blood cultures and IE induction success rate were significantly increased using 10 5 and 10 6 CFU compared to 10 4 CFU, there was no difference in blood cultures when comparing 10 5 and 10 6 CFU among wire injury (WI) + BC animals and IE induction rate plateaued after using 10 5 CFU. IE induction rate was 22% (10 4 CFU), 86% (10 5 CFU) and 92% (10 6 CFU) (Fig. 1 f). BC with 10 6 CFU induced the highest absolute and relative neutrophil counts compared to 10 4 and 10 5 CFU (p 0.001). The highest absolute and relative number of neutrophils was detected in the WI + BC group 1d after wire injury + bacterial challenge (213613 ± 40032 cells, 71,6% ± 8.7%, n = 18) (see supplements). The relative number of neutrophils was lower in all treatment groups (BC and WI + BC) with increasing distance from the bacterial challenge regardless of the bacterial concentration used (see supplements). There was neither a difference in absolute and relative blood cell counts between the different treatment groups (BC and WI + BC) nor in respect to the timing of the bacterial challenge after wire injury (24h vs 72h) (see supplements). Overall mortality for WI + BC mice was 13.8%, 80% of deaths occurred in WI + BC with 10 6 CFU. We further found peripheral abscess formation in WI + BC mice using 10 6 CFU. Since sepsis frequency and mortality were elevated in 10 6 CFU, while 10 5 CFU could reliably induce bacteremia and valvular infiltration, we proceeded using 10 5 CFU for our further investigations. To visually confirm and quantify bacterial valve infiltration and define its localization at different time points after infection we performed additional immunofluorescence microscopy using a S. aureus specific antibody (Fig. 1 i). Valvular S. aureus infiltration was increased in WI + BC mice at day 3 and 7 after bacterial challenge compared to BC only mice. We found a difference in S. aureus infiltration depending on the timing of bacterial challenge after wire injury (24h vs 72h) in WI + BC mice, favoring bacterial challenge after 72h (see supplements). Wire injury leads to AS development and causes endothelial damage To verify our hypothesis that increased IE induction in WI + BC compared to BC only was a result of prior endothelial damage, which is considered a precursor for IE we performed scanning electron microscopy (SEM). We observed endothelial damage and superficial fibrin depositions and bacterial infiltration in all WI + BC samples (6/6), while the endothelium was intact in all BC samples (6/6) (Fig. 2 a-c). Bacterial infiltration (violet) could be detected in areas of endothelial damage only (Fig. 2 e-f). Wire injury + bacterial challenge mice were prone to bacterial vegetation in transthoracic echocardiography One week after wire injury (3d after bacterial challenge), transthoracic echocardiography was conducted to assess AS, peak velocity, valvular colonization, and overall heart function. There was no difference in ejection fraction observed between WI + BC and BC mice (Table 1 ). Aortic peak velocity (Table 1 ) was increased in WI + BC compared to BC mice. Aortic regurgitation is a common complication of IE. Aortic regurgitation was present among BC animals in one mouse using 10 6 CFU (12.5%, n = 8). Among WI + BC mice we detected mild regurgitation in 75%, and moderate regurgitation in 12.5%, with no aortic regurgitation present in 12.5% of mice using 10 5 S. aureus (n = 8) (Fig. 3 A). After BC with 10 6 CFU aortic regurgitation was detectable in all WI + BC mice, 12.5% showed mild, 75% moderate and 12.5% severe signs of aortic regurgitation. To assess its impact on left-ventricular function we measured end-diastolic (EDV) and end-systolic volumes (ESV). Both ESV and EDV were increased in WI + BC mice compared to BC mice (Table 1 ). To assess aortic valve vegetation, we measured the AV cusp thickness in both parasternal long and short axis views. WI + BC mice showed thicker AV cusps compared to BC only mice (Table 1 + Fig. 3 b). There was no difference in AV cusp diameters comparing the 10 5 and 10 6 CFU bacterial concentrations. The largest vegetations were induced by 10 6 CFU S. aureus (1.16mm). Table 1 Echoardiographic analysis Left ventricular ejection fraction (LVEF), left ventricular volumes and fractional shortening (%) were measured in parasternal long-axis view after wire injury and bacterial challenge. ESV and EDV were increased in WI + BC mice after bacterial challenge in parasternal long axis view M-Mode. Aortic valve peak velocity was increased in WI + BC after undergoing wire injury. AV cusp diameter was increased in WI + BC mice after bacterial challenge as sign of additional valvular vegetation. Data is presented as mean ± SEM, and statistical significance was determined using unpaired one-way ANOVA. ∗∗∗P < 0.001; ∗∗P < 0.01; ∗P < 0.05. BC = bacterial challenge, WI = wire injury. Bacterial challenge after wire injury promotes valvular immune cell infiltration We performed immunofluorescence staining using CD45, CD68, and Ly6G (Fig. 4 ) to assess immune cell infiltration at day 1, 3, or 7 after bacterial challenge with 10 5 CFU. CD45 infiltration was higher in WI + BC mice after 3 and 7 days compared to BC mice (Fig. 4 a). Similar to this, the infiltration of CD68 + macrophages was increased in WI + BC mice, peaking at day 3 and 7 after wire injury compared to BC. However, CD68 + macrophage infiltration was already elevated in WI + BC compared to BC mice 1d after bacterial challenge (Fig. 4 b). WI + BC mice presented with significantly elevated Ly6G + neutrophil accumulation compared to BC animals 3d and 7d after bacterial challenge (Fig. 4 c). Discussion In this study, we successfully established a new aortic valve IE model combining a wire injury-induced endothelial damage model and i.v. bacterial challenge with S. aureus. It was our aim to mimic the situation of patients suffering from IE as closely as possible. To this end, we examined three different concentrations of S. aureus (10 4 , 10 5 , 10 6 CFU) at two different time points after wire injury (24h vs 72h). Wire injury showed distinctive features of endothelial damage in SEM, including fibrin depositions, that could serve as an ideal entry for S. aureus. Bacteremia and valvular infiltration of S. aureus was dose dependent with 10 6 CFU showing the highest titers, while bacterial challenge using 10 4 CFU showed the lowest bacterial blood titers and was thus unable to induce IE in a standardized way. The S. aureus (10 5–6 CFU) concentrations used to successfully induce IE were similar or lower to groups with different proposed IE models. Indeed, using the concentrations proposed in other studies we found higher mortality rates due to peripheral bacterial spreading including peripheral abscess formation and sepsis. These observations make it difficult to interpret immune cell responses as IE specific, especially when trying to potentially use early inflammation patterns as a prerequisite for IE detection using imaging techniques (Gibson, Kreuser et al. 2007, Ring, Hoerr et al. 2014, Liesenborghs, Meyers et al. 2019). Accounting for its high mortality rate 10 6 CFU as BC with high neutrophilia and yet similar bacterial vegetations proved to be more suitable for detecting severe endocarditis including sepsis compared to 10 5 CFU. Analysis of peripheral blood samples revealed neutrophilia after bacterial challenge in all groups, with WI + BC mice after 10 6 CFU showing the highest increase. These findings highlight that bacteria administration of 10 6 CFU must be carefully considered although it induces IE, the systemic effects differ from the situation in patients with IE of the aortic valve that exhibit local bacteria infiltration of the valves only (Bussani, De-Giorgio et al. 2019). As previously published data from our group indicate, we could detect AS one week after wire injury via echocardiography. After bacterial challenge we found an increase in aortic valve cusp diameter in-vivo as sign of bacterial vegetations, and an increase in aortic regurgitation frequency as well as severity, especially when using 10 6 CFU. These observations reflect the echocardiographic findings in patients suffering from IE (Maurer 2006 ). LV function was not impaired after bacterial challenge, volume overload due to aortic regurgitation was reflected in increased LV volumes, making this the first study to reliably characterize IE development in vivo via echocardiography. All immune cell markers (CD45, CD68 and Ly6G) were increased in WI + BC mice compared to BC mice. While CD45 and Ly6G positive immune cells showed peak concentrations after 3d and 7d, CD68 positive macrophages were already increased at day 1, suggesting an early response of infiltrating macrophages to IE. Other studies, using different IE models, have not yet investigated immune cell response in blood or valvular tissue (Gibson, Kreuser et al. 2007, Ring, Hoerr et al. 2014, Liesenborghs, Meyers et al. 2019). Our study is the first to investigate immune cell response in IE induction. Studies in human samples found similar cellular infiltration pattern as we did in our murine model, stressing the close link between our model and human pathophysiology (Kaiser, Joppich et al. 2022). Several murine models for IE have been published (Gibson, Kreuser et al. 2007, Meyers, Liesenborghs et al. 2018, Schwarz, Hoerr et al. 2020). Most models rely on inducing valvular damage by placing a catheter across the aortic valve and performing bacterial challenge afterwards with concentrations ranging between 10 5–6 CFU (Gibson, Kreuser et al. 2007, Meyers, Liesenborghs et al. 2018, Liesenborghs, Meyers et al. 2019, Schwarz, Hoerr et al. 2020). In these models the catheter scratches the endothelium with every heart beat in an uncontrolled manner. In our model, we benefit from the ultrasound controlled highly standardized wire injury model to damage the surface of the valves. In other models of IE, the observation period after bacterial challenge was limited to 3 days and bacteremia was performed simultaneously with wire placement (Gibson, Kreuser et al. 2007, Ring, Hoerr et al. 2014, Liesenborghs, Meyers et al. 2019). With our study we constructed a murine IE model that resembles the most common two-phasic pathophysiology of human IE consisting of an initial valvular damage followed by bacteremia after several hours and days. The striking differences between successful IE induction between WI + BC mice and BC mice highlights the significance of endothelial damage as a key requisite for IE induction and further underlines the proximity of our murine model in comparison with the human pathophysiology (Keynan and Rubinstein 2013 , Werdan, Dietz et al. 2014, Nappi, Martuscelli et al. 2022). Due to its experimental design certain limitations apply. Murine and human biology and its response to bacterial inflammation differ between species. Acute endothelial damage induction via wire injury differs from human AS development as a chronic condition, taking years to develop. The wire injury-based IE model established in this study provides a reliable, pathophysiological closely linked model of IE in wild-type mice to human IE. Different bacterial concentrations can be used to induce distinct severity grades of IE. To induce IE no genetic alterations or permanent wire must be placed, thus it can easily be applied to further analysis of immune cell responses and screen for biomarkers associated with early IE. All in all, this wire injury-based IE model may serve as an ideal tool to ameliorate our understanding of IE pathophysiology, the underlying immunological mechanisms and enhance the search for diagnostic biomarkers. Declarations Acknowledgements We thank Dr. Sandra Adler, Dr. Marta Stei, Dr. Stilla Frede, Gloria Martinac, Pia Fuchs and Jan Kleiner for excellent technical assistance. Funding BB was funded by BONFOR-Gerok-Grant (No.: O-109.0073). CKW was funded by the Deutsche Forschungsgemeinschaft (grant No.: 535107899), GN, SZ and CKW are funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Grant No. 397484323 – Project number 426093965. SZ and CKW are members of the excellence cluster ‘‘ImmunoSensation’’ at Bonn University. Ethics declaration Conflicts of interest The authors have no conflicts of interest to declare. There are no relationships with industry. During the preparation of this work the authors used CHAT-GPT in order to improve language. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. References Ahmed, S., et al. (2001). "Staphylococcus aureus fibronectin binding proteins are essential for internalization by osteoblasts but do not account for differences in intracellular levels of bacteria." 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Bartsch","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-3126-221X","institution":"Department of Internal Medicine-II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany","correspondingAuthor":true,"prefix":"","firstName":"Benedikt","middleName":"","lastName":"Bartsch","suffix":""},{"id":294650948,"identity":"c0d9b9b2-03bc-4079-b4b8-99dcef43954f","order_by":1,"name":"Ansgar Ackerschott","email":"","orcid":"","institution":"Department of Internal Medicine-II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany","correspondingAuthor":false,"prefix":"","firstName":"Ansgar","middleName":"","lastName":"Ackerschott","suffix":""},{"id":294650949,"identity":"200f6df9-1379-4564-b0a3-73179f51a283","order_by":2,"name":"Muntadher Al Zaidi","email":"","orcid":"","institution":"Department of Internal Medicine-II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany","correspondingAuthor":false,"prefix":"","firstName":"Muntadher","middleName":"Al","lastName":"Zaidi","suffix":""},{"id":294650950,"identity":"66228390-3254-4737-838c-f96043c726f1","order_by":3,"name":"Raul Nicolas Jamin","email":"","orcid":"","institution":"Department of Internal Medicine-II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany","correspondingAuthor":false,"prefix":"","firstName":"Raul","middleName":"Nicolas","lastName":"Jamin","suffix":""},{"id":294650951,"identity":"b214c1d7-6cba-4aa9-9bcc-a1d10577b813","order_by":4,"name":"Mariam Louis Fathy Nazir","email":"","orcid":"","institution":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany","correspondingAuthor":false,"prefix":"","firstName":"Mariam","middleName":"Louis Fathy","lastName":"Nazir","suffix":""},{"id":294650952,"identity":"aa6444b6-7424-409d-8f31-8278b1065135","order_by":5,"name":"Moritz Altrogge","email":"","orcid":"","institution":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany","correspondingAuthor":false,"prefix":"","firstName":"Moritz","middleName":"","lastName":"Altrogge","suffix":""},{"id":294650953,"identity":"6187ce7b-a534-4e11-bf92-d5c3883caa73","order_by":6,"name":"Lars Fester","email":"","orcid":"","institution":"Institute of Neuroanatomy of the University of Bonn, University Bonn, Bonn, Germany","correspondingAuthor":false,"prefix":"","firstName":"Lars","middleName":"","lastName":"Fester","suffix":""},{"id":294650954,"identity":"612272d6-7b84-4e5d-b20d-8e4da9b88b29","order_by":7,"name":"Jessica Lambertz","email":"","orcid":"","institution":"Institute of Neuroanatomy of the University of Bonn, University Bonn, Bonn, Germany","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"","lastName":"Lambertz","suffix":""},{"id":294650955,"identity":"79b810c0-6aa4-4a64-91cf-133663dc0fb4","order_by":8,"name":"Mark Coburn","email":"","orcid":"","institution":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany","correspondingAuthor":false,"prefix":"","firstName":"Mark","middleName":"","lastName":"Coburn","suffix":""},{"id":294650956,"identity":"2c610716-c155-4396-a317-959c3fb83de4","order_by":9,"name":"Georg Nickenig","email":"","orcid":"","institution":"Department of Internal Medicine-II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany","correspondingAuthor":false,"prefix":"","firstName":"Georg","middleName":"","lastName":"Nickenig","suffix":""},{"id":294650957,"identity":"d0bbf7db-102a-4289-8da5-d15d811ea002","order_by":10,"name":"Sebastian Zimmer","email":"","orcid":"","institution":"Department of Internal Medicine-II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany","correspondingAuthor":false,"prefix":"","firstName":"Sebastian","middleName":"","lastName":"Zimmer","suffix":""},{"id":294650958,"identity":"cd0fa4fa-eed8-4f55-a4ff-0da6812c6c72","order_by":11,"name":"Christina Katharina Weisheit","email":"data:image/png;base64,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","orcid":"","institution":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany","correspondingAuthor":true,"prefix":"","firstName":"Christina","middleName":"Katharina","lastName":"Weisheit","suffix":""}],"badges":[],"createdAt":"2024-04-23 15:37:17","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4313097/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4313097/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1371/journal.pone.0318955","type":"published","date":"2025-04-07T00:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55340963,"identity":"15d08419-7788-47a6-a307-ce3e3076eb32","added_by":"auto","created_at":"2024-04-26 02:08:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":481380,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eExperimental protocol and bacterial growth in mice after bacterial challenge\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e(a) Bacterial challenge was performed using 10\u003c/em\u003e\u003csup\u003e\u003cem\u003e4, \u003c/em\u003e\u003c/sup\u003e\u003cem\u003e10\u003c/em\u003e\u003csup\u003e\u003cem\u003e5\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e, and 10\u003c/em\u003e\u003csup\u003e\u003cem\u003e6\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e CFU for i.v. injection. Blood and valve samples were collected 24h after bacterial challenge and microbiologically examined. (b-d) Successful IE induction was determined 24h after bacterial challenge in %. CFU concentration in blood and valvular samples was measured 18h after incubation using agar. (e) Mice underwent wire injury (WI) to induce endothelial damage, bacterial challenge was performed either 24h or 72h after WI using 10\u003c/em\u003e\u003csup\u003e\u003cem\u003e4, \u003c/em\u003e\u003c/sup\u003e\u003cem\u003e10\u003c/em\u003e\u003csup\u003e\u003cem\u003e5\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e, and 10\u003c/em\u003e\u003csup\u003e\u003cem\u003e6\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e CFU, blood and valve samples were collected 24h and 72h after bacterial challenge. (f-h) Successful IE induction was determined 24h after bacterial challenge in %. CFU concentration in blood and valvular samples was measured 18h after incubation using agar. (i) Immunofluorescence microscopy for was performed after mice were sacrificed and stained for S. aureus. Data in the quantitative plots are presented as mean ± SEM, and statistical significance was determined using unpaired one-way ANOVA. ∗∗∗P \u0026lt; 0.001; ∗∗P \u0026lt; 0.01; ∗P \u0026lt; 0.05. BC= bacterial challenge.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-4313097/v1/928caf01703ad64fb500f33a.png"},{"id":55340973,"identity":"3ab5f3db-14fc-42e0-b946-30e4eacf0444","added_by":"auto","created_at":"2024-04-26 02:08:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1148507,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eScanning electron microscopy after bacterial challenge\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e(a-c) Scanning electron microscopy images (2.00 KV LEI, 14mm WD) of aortic valve leaflet cross-sections of BC animals three days after bacterial challenge. The endothelial layer is intact and bacterial infiltration is not present. (d-f) Wire injury causes endothelial damage with only few endothelial cells remaining (EC) and enables S. aureus (S.a., violet) infiltration via fibrin layers and activated platelets (AP). BC= bacterial challenge, WI= wire injury.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTo verify our hypothesis that increased IE induction in WI + BC compared to BC only was a result of prior endothelial damage, which is considered a precursor for IE we performed scanning electron microscopy (SEM). We observed endothelial damage and superficial fibrin depositions and bacterial infiltration in all WI + BC samples (6/6), while the endothelium was intact in all BC samples (6/6) (Fig. 2a-c). Bacterial infiltration (violet) could be detected in areas of endothelial damage only (Fig. 2e-f).\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-4313097/v1/dc74998f29b605380496f3ff.png"},{"id":55341537,"identity":"7a975fd0-bd45-4373-9a8e-abb073cabf66","added_by":"auto","created_at":"2024-04-26 02:16:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":536274,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAortic regurgitation and bacterial infiltration in infective endocarditis\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e(a) Aortic regurgitation was more prevalent in mice after wire injury and bacterial challenge. (b) Exemplary aortic valve endocarditis vegetations in parasternal long-axis view after wire injury and bacterial challenge.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-4313097/v1/6631ae2bf53550c182808ac4.png"},{"id":55340967,"identity":"4f3cfad1-b994-4138-a155-8bf1664373a0","added_by":"auto","created_at":"2024-04-26 02:08:13","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":625209,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eImmunofluorescence staining\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e(a-c) Immunofluorescence microscopy was performed after mice were sacrificed and the hearts were collected. Representative images and quantitative analysis of CD45 (a), CD68 (b), Ly6G (c) in WI + BC mice. Data in the quantitative plots are presented as mean ± SEM, and statistical significance was determined using unpaired one-way ANOVA. ∗∗∗P \u0026lt; 0.001; ∗∗P \u0026lt; 0.01; ∗P \u0026lt; 0.05. BC= bacterial challenge, WI= wire injury.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-4313097/v1/3ec6250e7104914c7b98792c.png"},{"id":80648420,"identity":"43e112ea-c27f-485e-a746-8073ef4d5618","added_by":"auto","created_at":"2025-04-15 14:28:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4004962,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4313097/v1/41c2d037-130c-4a42-85d6-c7aef1e6affc.pdf"},{"id":55340965,"identity":"054c9943-03e4-4a07-8fd1-462c9002c472","added_by":"auto","created_at":"2024-04-26 02:08:13","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":875592,"visible":true,"origin":"","legend":"","description":"","filename":"SIEndokarditis.docx","url":"https://assets-eu.researchsquare.com/files/rs-4313097/v1/5e8634d35027a2a808928e0d.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eA novel murine model of infective endocarditis mimics human pathophysiology\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eInfective endocarditis (IE) is defined as a bacterial infection of the heart, most commonly affecting the heart valves (van den Brink, Swaans et al. 2017). Its incidence is increasing in developed countries, and it has high mortality rates of up to 30% (Tackling and Lala \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2019\u003c/span\u003e, Delgado, Ajmone Marsan et al. 2023). Despite optimal medical therapy and a trend towards early surgical intervention, mortality rates remain high (Cahill, Baddour et al. 2017). Major complications include septic stroke or acute heart failure (Cahill, Baddour et al. 2017, Delgado, Ajmone Marsan et al. 2023).Patients initially present with only mild symptoms and no direct IE-specific surrogates; echocardiography, CT or PET-CT scans are often inconclusive, hindering early diagnosis and treatment (Delgado, Ajmone Marsan et al. 2023). Risk factors for IE include cardiac procedures such as valve replacement or pre-existing innate or degenerative valvular disease (Vahanian, Beyersdorf et al. 2022, Delgado, Ajmone Marsan et al. 2023). The most common bacteria causing IE in developed countries is Staphylococcus aureus (S. aureus), and its incidence is increasing (van den Brink, Swaans et al. 2017). The aortic valve is the most commonly affected valve in IE due to the prevalence of aortic valve stenosis (AS) in the elderly with up to 2% (Goody, Hosen et al. 2020, Luehr, Bauernschmitt et al. 2020). While its progression is often slow and asymptotic, severe AS has a mortality rate in the range of 50% if untreated (Otto and Prendergast \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2014\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur understanding of the mechanisms that cause IE and inflammatory responses is still limited. Bacteriemia is considered a precursor of both native and prosthetic IE (Werdan, Dietz et al. 2014, Iung \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2019\u003c/span\u003e, Liesenborghs, Meyers et al. 2020). Healthy heart valves have a natural barrier to bacterial adhesion and infiltration consisting of an intact endothelial layer, making patients with previous valvular pathology such as stenosis or rheumatic fever susceptible to bacterial metastasis due to a potential lack of endothelial protection (Werdan, Dietz et al. 2014). While pre-existing valvular pathologies are common among IE patients, only few patients with pre-existing valvular pathologies develop IE, demonstrating a need to better understand the early pathophysiology of IE induction (Bussani, De-Giorgio et al. 2019).\u003c/p\u003e \u003cp\u003eEndothelial damage exposes the underlying tissue of collagen matrix and interstitial cells to the bloodstream, resulting in fibrin and von Willebrand factor (vWF) adhesion and platelet activation, leading to microthrombotic lesions (Liesenborghs, Meyers et al. 2019). During episodes of bacteremia, these lesions act as gateways for bacterial infiltration. S. aureus expresses abundant adhesive surface proteins, making it an ideal pathogen to infiltrate valves with prior endothelial damage (Ahmed, Meghji et al. 2001). After valve infiltration, S. aureus promotes further platelet activation with its surface proteins (McDevitt, Francois et al. 1995). Platelet activation is facilitated by soluble fibrin within damaged valves, which creates a protective shield that impedes immune cell infiltration and serves as an ideal environment for bacterial adhesion (Fitzgerald, Foster and Cox 2006, Liesenborghs, Meyers et al. 2019). While further direct immune cell interaction with the bacteria is impeded by the fibrin-platelet coat, monocytes, macrophages and neutrophils were shown to infiltrate IE valves (Kaiser, Joppich et al. 2022). IE patients often show an increase of neutrophils in peripheral blood counts which normalizes after treatment initation. To further evade the immune response, S. aureus can infiltrate both, endothelial cells and fibroblasts using FnBPs (Werdan, Dietz et al. 2014). Intracellularly, it can release toxins and exoenzymes, including α-hemolysin, which can induce cell death and further aggravate valve damage (Hocke, Temmesfeld-Wollbrueck et al. 2006). Alternatively, once intracellular, S. aureus can switch between slow and fast metabolism depending on environmental changes, resulting in chronic and therapy-resistant infections (Proctor, Von Eiff et al. 2006).\u003c/p\u003e \u003cp\u003eTo date, existing murine models of IE either lacked an adequate immune response, making quantification or localization analysis difficult, or exhibited signs of fulminant septic shock, including valvular abscess formation (Gibson, Kreuser et al. 2007, Ring, Hoerr et al. 2014, Liesenborghs, Meyers et al. 2019). To date, most models rely on either a single i.v. injection (between 10\u003csup\u003e5\u0026ndash;7\u003c/sup\u003e CFU) of bacteria or permanent placement of a 32-G catheter across the aortic valve, ignoring the most common clinical setting in which IE develops within pre-existing endothelial damage of the heart valves (e.g., AS). We have recently introduced a novel murine model of AS, which allows us to reliably induce AS in mice (Niepmann, Steffen et al. 2019). In this study, we aim to establish a murine model of IE that mimics the most common clinical setting: endothelial damage followed by bacteremia via i.v. S. aureus injection.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eMice\u003c/p\u003e \u003cp\u003eThe mice used in this study were male and female C57BL/6-J (wild-type), aged between 10 to 12 weeks, and obtained from Janvier Labs, France. The animals were provided with ad libitum access to drinking water and food. The room in which the mice were kept maintained a temperature of 22\u0026deg;C and followed a 12-hour light cycle. The study was conducted in accordance with the guidelines set by the Animal Ethics Committee of the North Rhine-Westphalian State Agency for Nature, Environment, and Consumer Protection in Germany (AZ 81-02.04.2020.A174).\u003c/p\u003e \u003cp\u003eEchocardiography\u003c/p\u003e \u003cp\u003eFor the assessment of valvular function, mice were sedated with 1.5% isoflurane under strict surveillance of respiratory rate, electrocardiogram, and body temperature. Aortic valve peak velocity, aortic regurgitation, and bacterial valve vegetations were measured in the suprasternal view. Other standard echocardiographic parameters such as left ventricular ejection fraction, fractional shortening, and ventricular volumes were measured in the parasternal long-axis views. Regurgitation jets of the aortic valve were defined as follows: in immediate proximity to the aortic valve: mild; if jets reached the length of the left ventricular outflow tract: moderate; and if jets reached beyond the outflow tract: severe.\u003c/p\u003e \u003cp\u003eWire injury\u003c/p\u003e \u003cp\u003eThe wire injury procedure was conducted following a recently published protocol from our facility (Niepmann et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). In brief, mice were anesthetized using an intraperitoneal injection of 150 mg/kg Ketamine and 16 mg/kg Xylazine. The right carotid artery was surgically accessed, and a straight guidewire with a shortened and soldered tip (Abbott HI-TORQUE 0.014) was used. Blood flow was halted with the application of two ligatures. Echocardiography was employed to confirm the correct placement of the inserted wire into the left ventricle through the trans-aortic valve.\u003c/p\u003e \u003cp\u003eTo induce endothelial damage, the wire was moved back and forth across the valve 50 times and rotated 100 times. During the procedure, echocardiography was immediately performed to ensure that no aortic regurgitation occurred. Subsequently, the wire was removed, and the artery was ligated.\u003c/p\u003e \u003cp\u003eBacterial challenge and cultivation\u003c/p\u003e \u003cp\u003eThe methicillin-susceptible S. aureus strain SA-LT 68/03C12Y7, isolated from human samples, was preserved at -80\u0026deg;C in 20% glycerol. To create the bacterial challenge suspension, S. aureus was cultured with LB media for 8 hours at 37\u0026deg;C, using a slow, pivoting motion. Subsequently, the bacteria were suspended in sterile 0.9% NaCl to reach a concentration of 10\u003csup\u003e4\u0026ndash;6\u003c/sup\u003e CFU/100 \u0026micro;l. Prior to the experiment, the appropriate bacterial volumes were confirmed by inoculating 10 \u0026micro;l of bacteria on 5% blood agar plates (BD Biosciences). The bacterial challenge was carried out either 1 day or 3 days after the wire injury by intravenously injecting 0.1 ml of the bacterial suspension. After injection S. aureus blood cultures were collected from the animals and cultivated on 5% blood agar plates.\u003c/p\u003e \u003cp\u003eHistological preparation\u003c/p\u003e \u003cp\u003eMice were euthanized via cervical dislocation 1d, 3d, or 7d after the bacterial challenge. Hearts were extracted using sterile instruments and were flushed with sterile 0.9% saline solution. Hearts where then either purified using Precellys\u0026reg; or made available to immunofluorescence. Under a light microscope magnification of 10x, the hearts were opened by making a sagittal incision along the left ventricular outflow tract. Any remaining blood clots were eliminated using sterile 0.9% saline solution. CD68 and CD45 staining was used to visualize immune cell and macrophage infiltration of the aortic valve as described in Niepmann et al \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2019\u003c/span\u003e. For Ly6G staining, aortic valve sections were fixed in Acetone for 30 min and blocked with 10% normal goat serum (NGS). The primary antibody was diluted 1:200 (anti Ly6G, rat 1A8 anti mouse, BD Biosciences, USA) and incubated overnight. The secondary antibody was diluted 1:500 (Cy3 AffiniPure Donkey anti Rat IgG, Jackson ImmunoResearch Laboratories Inc) and incubated for 90 minutes. For S. aureus staining, aortic valve sections were fixed in 0.1% Saponin for 30 min and blocked with 10% NGS. The primary antibody was diluted 1:200 (Anti-S. aureus IgG rabbit, ab20920, Abcam, UK) and incubated overnight. The secondary antibody was diluted 1:1000 (AlexaFluor 647, goat anti rabbit, ThermoFisher Scientific, USA) and incubated for 1h. NucBlue\u0026trade; (DAPI) (ThermoFisher Scientific, USA) was used for counterstaining of the nuclei.\u003c/p\u003e \u003cp\u003eFlow cytometry\u003c/p\u003e \u003cp\u003eFor quantification of immune responses, 50 \u0026micro;l of whole blood was collected. Red blood cells were filtered, and Fc receptors were blocked (Fc-Block, Pharmingen). After washing, cells were stained using anti-Ly6G (BioLegend), anti-B220 (BioLegend), anti-CD11b (BioLegend), anti-CD3 (eBioscience), CD45 (BioLegend) and anti NK1.1 (BioLegend). For flow cytometry we used FACSCanto II (BD Bioscience, Franklin Lakes, USA) and analyzed the data with FlowJo (Tree Star, Ashland, USA).\u003c/p\u003e \u003cp\u003eScanning electron microscopy (SEM)\u003c/p\u003e \u003cp\u003eSamples underwent fixation through transcardiac perfusion with 6% glutaraldehyde in phosphate buffer. For preparation in scanning electron microscopy, the samples were rinsed in phosphate buffer and subsequently post-fixed in 2% osmium tetroxide in phosphate buffer for 2 hours at room temperature. Dehydration was achieved using a graded ethanol series, followed by a transition to acetone. Afterward, this intermediate step was eliminated using a critical point dryer, and a coating of 8 nm of platinum was applied using a sputter coater, prior to visualization using a scanning electron microscope (Jeol 7500F).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe data presented is shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM. Appropriate assumptions of data (e.g. normal distribution or similar variation between experimental groups) were examined before statistical tests were conducted. The number of experiments and the number of mice per group are provided in the figure legends. Student\u0026rsquo;s t-tests were used whenever two groups were compared, and one-way or two-way analyses of variance followed by Tukey\u0026rsquo;s test for multiple comparisons. The analysis was performed with Prism 8 (GraphPad Software, Inc. La Jolla, CA). The results are provided as mean unless noted otherwise; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eWire injury\u0026thinsp;+\u0026thinsp;bacterial challenge mice showed increased bacteremia and valvular infiltration levels of S. aureus\u003c/p\u003e\n\u003cp\u003eSince bacteremia is considered a necessary precursor in IE development, we first tested bacterial challenge via intravenous injection in wild-type C57BL/6-J mice using 10\u003csup\u003e4\u003c/sup\u003e, 10\u003csup\u003e5\u003c/sup\u003e and 10\u003csup\u003e6\u003c/sup\u003e CFU S. aureus for spontaneous development of IE (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ea). Blood cultures and cultures from valvular samples revealed dose dependent blood bacterial titers and valvular bacterial colonies (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eb\u0026thinsp;+\u0026thinsp;c). The overall success rate of IE induction confirmed with valvular cultures was 22% (10\u003csup\u003e4\u003c/sup\u003e CFU), 27% (10\u003csup\u003e5\u003c/sup\u003e CFU) and 67% (10\u003csup\u003e6\u003c/sup\u003e CFU) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ed). Mortality in mice with bacterial challenge (BC) only was 4.5%. Mice receiving 10\u003csup\u003e6\u003c/sup\u003e CFU bacterial challenge suffered severe morbidity including peripheral abscess formation and clinical signs of sepsis including weight loss, reduced mobility and decreased fur grooming.\u003c/p\u003e\n\u003cp\u003eThe immunological response following bacterial challenge using concentrations of 10\u003csup\u003e5\u003c/sup\u003e and 10\u003csup\u003e6\u003c/sup\u003e CFU was verified by increased neutrophil counts. Both relative and absolute neutrophil counts were higher when bacterial challenge was performed using 10\u003csup\u003e6\u003c/sup\u003e CFU (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In contrast, the number of B- and T-cells was reduced using 10\u003csup\u003e6\u003c/sup\u003e CFU (p\u0026thinsp;\u0026gt;\u0026thinsp;0.001) (Online Resource 1).\u003c/p\u003e\n\u003cp\u003eBecause a singular bacterial challenge at concentrations below the sepsis threshold was unreliable in inducing endocarditis, we extended our experimental protocol to include a wire injury of the aortic valve before bacterial challenge to create endothelial damage, which we hypothesized to increase the likelihood of endocarditis (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ee). Bacterial challenge was performed either 24h or 72h after wire injury. Blood cultures and cultures from valvular samples revealed dose dependent blood bacterial titers and valvular bacterial colonies (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eg\u0026thinsp;+\u0026thinsp;h). While blood cultures and IE induction success rate were significantly increased using 10\u003csup\u003e5\u003c/sup\u003e and 10\u003csup\u003e6\u003c/sup\u003e CFU compared to 10\u003csup\u003e4\u003c/sup\u003e CFU, there was no difference in blood cultures when comparing 10\u003csup\u003e5\u003c/sup\u003e and 10\u003csup\u003e6\u003c/sup\u003e CFU among wire injury (WI)\u0026thinsp;+\u0026thinsp;BC animals and IE induction rate plateaued after using 10\u003csup\u003e5\u003c/sup\u003e CFU. IE induction rate was 22% (10\u003csup\u003e4\u003c/sup\u003e CFU), 86% (10\u003csup\u003e5\u003c/sup\u003e CFU) and 92% (10\u003csup\u003e6\u003c/sup\u003e CFU) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ef).\u003c/p\u003e\n\u003cp\u003eBC with 10\u003csup\u003e6\u003c/sup\u003e CFU induced the highest absolute and relative neutrophil counts compared to 10\u003csup\u003e4\u003c/sup\u003e and 10\u003csup\u003e5\u003c/sup\u003e CFU (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in WI\u0026thinsp;+\u0026thinsp;BC mice. In contrast, the number of B- and T-cells was reduced using 10\u003csup\u003e6\u003c/sup\u003e CFU (p\u0026thinsp;\u0026gt;\u0026thinsp;0.001). The highest absolute and relative number of neutrophils was detected in the WI\u0026thinsp;+\u0026thinsp;BC group 1d after wire injury\u0026thinsp;+\u0026thinsp;bacterial challenge (213613\u0026thinsp;\u0026plusmn;\u0026thinsp;40032 cells, 71,6% \u0026plusmn; 8.7%, n\u0026thinsp;=\u0026thinsp;18) (see supplements). The relative number of neutrophils was lower in all treatment groups (BC and WI\u0026thinsp;+\u0026thinsp;BC) with increasing distance from the bacterial challenge regardless of the bacterial concentration used (see supplements). There was neither a difference in absolute and relative blood cell counts between the different treatment groups (BC and WI\u0026thinsp;+\u0026thinsp;BC) nor in respect to the timing of the bacterial challenge after wire injury (24h vs 72h) (see supplements).\u003c/p\u003e\n\u003cp\u003eOverall mortality for WI\u0026thinsp;+\u0026thinsp;BC mice was 13.8%, 80% of deaths occurred in WI\u0026thinsp;+\u0026thinsp;BC with 10\u003csup\u003e6\u003c/sup\u003e CFU. We further found peripheral abscess formation in WI\u0026thinsp;+\u0026thinsp;BC mice using 10\u003csup\u003e6\u003c/sup\u003e CFU. Since sepsis frequency and mortality were elevated in 10\u003csup\u003e6\u003c/sup\u003e CFU, while 10\u003csup\u003e5\u003c/sup\u003e CFU could reliably induce bacteremia and valvular infiltration, we proceeded using 10\u003csup\u003e5\u003c/sup\u003e CFU for our further investigations.\u003c/p\u003e\n\u003cp\u003eTo visually confirm and quantify bacterial valve infiltration and define its localization at different time points after infection we performed additional immunofluorescence microscopy using a S. aureus specific antibody (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ei). Valvular S. aureus infiltration was increased in WI\u0026thinsp;+\u0026thinsp;BC mice at day 3 and 7 after bacterial challenge compared to BC only mice. We found a difference in S. aureus infiltration depending on the timing of bacterial challenge after wire injury (24h vs 72h) in WI\u0026thinsp;+\u0026thinsp;BC mice, favoring bacterial challenge after 72h (see supplements).\u003c/p\u003e\n\u003cp\u003eWire injury leads to AS development and causes endothelial damage\u003c/p\u003e\n\u003cp\u003eTo verify our hypothesis that increased IE induction in WI\u0026thinsp;+\u0026thinsp;BC compared to BC only was a result of prior endothelial damage, which is considered a precursor for IE we performed scanning electron microscopy (SEM). We observed endothelial damage and superficial fibrin depositions and bacterial infiltration in all WI\u0026thinsp;+\u0026thinsp;BC samples (6/6), while the endothelium was intact in all BC samples (6/6) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ea-c). Bacterial infiltration (violet) could be detected in areas of endothelial damage only (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ee-f).\u003c/p\u003e\n\u003cp\u003eWire injury\u0026thinsp;+\u0026thinsp;bacterial challenge mice were prone to bacterial vegetation in transthoracic echocardiography\u003c/p\u003e\n\u003cp\u003eOne week after wire injury (3d after bacterial challenge), transthoracic echocardiography was conducted to assess AS, peak velocity, valvular colonization, and overall heart function. There was no difference in ejection fraction observed between WI\u0026thinsp;+\u0026thinsp;BC and BC mice (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Aortic peak velocity (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) was increased in WI\u0026thinsp;+\u0026thinsp;BC compared to BC mice. Aortic regurgitation is a common complication of IE. Aortic regurgitation was present among BC animals in one mouse using 10\u003csup\u003e6\u003c/sup\u003e CFU (12.5%, n\u0026thinsp;=\u0026thinsp;8). Among WI\u0026thinsp;+\u0026thinsp;BC mice we detected mild regurgitation in 75%, and moderate regurgitation in 12.5%, with no aortic regurgitation present in 12.5% of mice using 10\u003csup\u003e5\u003c/sup\u003e S. aureus (n\u0026thinsp;=\u0026thinsp;8) (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA). After BC with 10\u003csup\u003e6\u003c/sup\u003e CFU aortic regurgitation was detectable in all WI\u0026thinsp;+\u0026thinsp;BC mice, 12.5% showed mild, 75% moderate and 12.5% severe signs of aortic regurgitation. To assess its impact on left-ventricular function we measured end-diastolic (EDV) and end-systolic volumes (ESV). Both ESV and EDV were increased in WI\u0026thinsp;+\u0026thinsp;BC mice compared to BC mice (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eTo assess aortic valve vegetation, we measured the AV cusp thickness in both parasternal long and short axis views. WI\u0026thinsp;+\u0026thinsp;BC mice showed thicker AV cusps compared to BC only mice (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026thinsp;+\u0026thinsp;Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eb). There was no difference in AV cusp diameters comparing the 10\u003csup\u003e5\u003c/sup\u003e and 10\u003csup\u003e6\u003c/sup\u003e CFU bacterial concentrations. The largest vegetations were induced by 10\u003csup\u003e6\u003c/sup\u003e CFU S. aureus (1.16mm).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTable 1 Echoardiographic analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" width=\"640\" height=\"508\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLeft ventricular ejection fraction (LVEF), left ventricular volumes and fractional shortening (%) were measured in parasternal long-axis view after wire injury and bacterial challenge. ESV and EDV were increased in WI\u0026thinsp;+\u0026thinsp;BC mice after bacterial challenge in parasternal long axis view M-Mode. Aortic valve peak velocity was increased in WI\u0026thinsp;+\u0026thinsp;BC after undergoing wire injury. AV cusp diameter was increased in WI\u0026thinsp;+\u0026thinsp;BC mice after bacterial challenge as sign of additional valvular vegetation. Data is presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM, and statistical significance was determined using unpaired one-way ANOVA. \u0026lowast;\u0026lowast;\u0026lowast;P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; \u0026lowast;\u0026lowast;P\u0026thinsp;\u0026lt;\u0026thinsp;0.01; \u0026lowast;P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. BC\u0026thinsp;=\u0026thinsp;bacterial challenge, WI\u0026thinsp;=\u0026thinsp;wire injury.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBacterial challenge after wire injury promotes valvular immune cell infiltration\u003c/p\u003e\n\u003cp\u003eWe performed immunofluorescence staining using CD45, CD68, and Ly6G (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e) to assess immune cell infiltration at day 1, 3, or 7 after bacterial challenge with 10\u003csup\u003e5\u003c/sup\u003e CFU. CD45 infiltration was higher in WI\u0026thinsp;+\u0026thinsp;BC mice after 3 and 7 days compared to BC mice (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003ea). Similar to this, the infiltration of CD68\u003csup\u003e+\u003c/sup\u003e macrophages was increased in WI\u0026thinsp;+\u0026thinsp;BC mice, peaking at day 3 and 7 after wire injury compared to BC. However, CD68\u003csup\u003e+\u003c/sup\u003e macrophage infiltration was already elevated in WI\u0026thinsp;+\u0026thinsp;BC compared to BC mice 1d after bacterial challenge (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eb). WI\u0026thinsp;+\u0026thinsp;BC mice presented with significantly elevated Ly6G\u003csup\u003e+\u003c/sup\u003e neutrophil accumulation compared to BC animals 3d and 7d after bacterial challenge (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003ec).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we successfully established a new aortic valve IE model combining a wire injury-induced endothelial damage model and i.v. bacterial challenge with S. aureus. It was our aim to mimic the situation of patients suffering from IE as closely as possible. To this end, we examined three different concentrations of S. aureus (10\u003csup\u003e4\u003c/sup\u003e, 10\u003csup\u003e5\u003c/sup\u003e, 10\u003csup\u003e6\u003c/sup\u003e CFU) at two different time points after wire injury (24h vs 72h).\u003c/p\u003e \u003cp\u003eWire injury showed distinctive features of endothelial damage in SEM, including fibrin depositions, that could serve as an ideal entry for S. aureus. Bacteremia and valvular infiltration of S. aureus was dose dependent with 10\u003csup\u003e6\u003c/sup\u003e CFU showing the highest titers, while bacterial challenge using 10\u003csup\u003e4\u003c/sup\u003e CFU showed the lowest bacterial blood titers and was thus unable to induce IE in a standardized way. The S. aureus (10\u003csup\u003e5\u0026ndash;6\u003c/sup\u003e CFU) concentrations used to successfully induce IE were similar or lower to groups with different proposed IE models. Indeed, using the concentrations proposed in other studies we found higher mortality rates due to peripheral bacterial spreading including peripheral abscess formation and sepsis. These observations make it difficult to interpret immune cell responses as IE specific, especially when trying to potentially use early inflammation patterns as a prerequisite for IE detection using imaging techniques (Gibson, Kreuser et al. 2007, Ring, Hoerr et al. 2014, Liesenborghs, Meyers et al. 2019). Accounting for its high mortality rate 10\u003csup\u003e6\u003c/sup\u003e CFU as BC with high neutrophilia and yet similar bacterial vegetations proved to be more suitable for detecting severe endocarditis including sepsis compared to 10\u003csup\u003e5\u003c/sup\u003e CFU.\u003c/p\u003e \u003cp\u003eAnalysis of peripheral blood samples revealed neutrophilia after bacterial challenge in all groups, with WI\u0026thinsp;+\u0026thinsp;BC mice after 10\u003csup\u003e6\u003c/sup\u003e CFU showing the highest increase. These findings highlight that bacteria administration of 10\u003csup\u003e6\u003c/sup\u003e CFU must be carefully considered although it induces IE, the systemic effects differ from the situation in patients with IE of the aortic valve that exhibit local bacteria infiltration of the valves only (Bussani, De-Giorgio et al. 2019).\u003c/p\u003e \u003cp\u003eAs previously published data from our group indicate, we could detect AS one week after wire injury via echocardiography. After bacterial challenge we found an increase in aortic valve cusp diameter \u003cem\u003ein-vivo\u003c/em\u003e as sign of bacterial vegetations, and an increase in aortic regurgitation frequency as well as severity, especially when using 10\u003csup\u003e6\u003c/sup\u003e CFU. These observations reflect the echocardiographic findings in patients suffering from IE (Maurer \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). LV function was not impaired after bacterial challenge, volume overload due to aortic regurgitation was reflected in increased LV volumes, making this the first study to reliably characterize IE development \u003cem\u003ein vivo\u003c/em\u003e via echocardiography. All immune cell markers (CD45, CD68 and Ly6G) were increased in WI\u0026thinsp;+\u0026thinsp;BC mice compared to BC mice. While CD45 and Ly6G positive immune cells showed peak concentrations after 3d and 7d, CD68 positive macrophages were already increased at day 1, suggesting an early response of infiltrating macrophages to IE. Other studies, using different IE models, have not yet investigated immune cell response in blood or valvular tissue (Gibson, Kreuser et al. 2007, Ring, Hoerr et al. 2014, Liesenborghs, Meyers et al. 2019). Our study is the first to investigate immune cell response in IE induction. Studies in human samples found similar cellular infiltration pattern as we did in our murine model, stressing the close link between our model and human pathophysiology (Kaiser, Joppich et al. 2022).\u003c/p\u003e \u003cp\u003eSeveral murine models for IE have been published (Gibson, Kreuser et al. 2007, Meyers, Liesenborghs et al. 2018, Schwarz, Hoerr et al. 2020). Most models rely on inducing valvular damage by placing a catheter across the aortic valve and performing bacterial challenge afterwards with concentrations ranging between 10\u003csup\u003e5\u0026ndash;6\u003c/sup\u003e CFU (Gibson, Kreuser et al. 2007, Meyers, Liesenborghs et al. 2018, Liesenborghs, Meyers et al. 2019, Schwarz, Hoerr et al. 2020). In these models the catheter scratches the endothelium with every heart beat in an uncontrolled manner. In our model, we benefit from the ultrasound controlled highly standardized wire injury model to damage the surface of the valves.\u003c/p\u003e \u003cp\u003eIn other models of IE, the observation period after bacterial challenge was limited to 3 days and bacteremia was performed simultaneously with wire placement (Gibson, Kreuser et al. 2007, Ring, Hoerr et al. 2014, Liesenborghs, Meyers et al. 2019). With our study we constructed a murine IE model that resembles the most common two-phasic pathophysiology of human IE consisting of an initial valvular damage followed by bacteremia after several hours and days. The striking differences between successful IE induction between WI\u0026thinsp;+\u0026thinsp;BC mice and BC mice highlights the significance of endothelial damage as a key requisite for IE induction and further underlines the proximity of our murine model in comparison with the human pathophysiology (Keynan and Rubinstein \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2013\u003c/span\u003e, Werdan, Dietz et al. 2014, Nappi, Martuscelli et al. 2022).\u003c/p\u003e \u003cp\u003eDue to its experimental design certain limitations apply. Murine and human biology and its response to bacterial inflammation differ between species. Acute endothelial damage induction via wire injury differs from human AS development as a chronic condition, taking years to develop.\u003c/p\u003e \u003cp\u003eThe wire injury-based IE model established in this study provides a reliable, pathophysiological closely linked model of IE in wild-type mice to human IE. Different bacterial concentrations can be used to induce distinct severity grades of IE. To induce IE no genetic alterations or permanent wire must be placed, thus it can easily be applied to further analysis of immune cell responses and screen for biomarkers associated with early IE. All in all, this wire injury-based IE model may serve as an ideal tool to ameliorate our understanding of IE pathophysiology, the underlying immunological mechanisms and enhance the search for diagnostic biomarkers.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Dr. Sandra Adler, Dr. Marta Stei, Dr. Stilla Frede, Gloria Martinac, Pia Fuchs and Jan Kleiner for excellent technical assistance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBB was funded by BONFOR-Gerok-Grant (No.: O-109.0073). CKW was funded by the Deutsche Forschungsgemeinschaft (grant No.: 535107899), GN, SZ and CKW are funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) \u0026ndash; Grant No. 397484323 \u0026ndash; Project number 426093965. SZ and CKW are members of the excellence cluster \u0026lsquo;\u0026lsquo;ImmunoSensation\u0026rsquo;\u0026rsquo; at Bonn University.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare. There are no relationships with industry.\u003c/p\u003e\n\u003cp\u003eDuring the preparation of this work the authors used CHAT-GPT in order to improve language. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAhmed, S., et al. (2001). \u0026quot;Staphylococcus aureus fibronectin binding proteins are essential for internalization by osteoblasts but do not account for differences in intracellular levels of bacteria.\u0026quot; Infection and immunity \u003cstrong\u003e69\u003c/strong\u003e(5): 2872-2877.\u003c/li\u003e\n\u003cli\u003eBussani, R., et al. (2019). \u0026quot;Overview and comparison of infectious endocarditis and non-infectious endocarditis: a review of 814 autoptic cases.\u0026quot; In vivo \u003cstrong\u003e33\u003c/strong\u003e(5): 1565-1572.\u003c/li\u003e\n\u003cli\u003eCahill, T. J., et al. (2017). \u0026quot;Challenges in infective endocarditis.\u0026quot; Journal of the American College of Cardiology \u003cstrong\u003e69\u003c/strong\u003e(3): 325-344.\u003c/li\u003e\n\u003cli\u003eDelgado, V., et al. (2023). \u0026quot;2023 ESC Guidelines for the management of endocarditis: Developed by the task force on the management of endocarditis of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Nuclear Medicine (EANM).\u0026quot; European Heart Journal \u003cstrong\u003e44\u003c/strong\u003e(39): 3948-4042.\u003c/li\u003e\n\u003cli\u003eFitzgerald, J. R., et al. (2006). \u0026quot;The interaction of bacterial pathogens with platelets.\u0026quot; Nature Reviews Microbiology \u003cstrong\u003e4\u003c/strong\u003e(6): 445-457.\u003c/li\u003e\n\u003cli\u003eGibson, G. W., et al. (2007). \u0026quot;Development of a mouse model of induced Staphylococcus aureus infective endocarditis.\u0026quot; Comparative medicine \u003cstrong\u003e57\u003c/strong\u003e(6): 563-569.\u003c/li\u003e\n\u003cli\u003eGoody, P. R., et al. 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(2022). \u0026quot;Immunothrombotic Signatures of Resident and Circulating Immune Cells in Human Infective Endocarditis Revealed By Multi-Omic Profiling.\u0026quot; Blood \u003cstrong\u003e140\u003c/strong\u003e(Supplement 1): 2591-2592.\u003c/li\u003e\n\u003cli\u003eKeynan, Y. and E. Rubinstein (2013). \u0026quot;Pathophysiology of infective endocarditis.\u0026quot; Current infectious disease reports \u003cstrong\u003e15\u003c/strong\u003e: 342-346.\u003c/li\u003e\n\u003cli\u003eLiesenborghs, L., et al. (2019). \u0026quot;Staphylococcus aureus endocarditis: distinct mechanisms of bacterial adhesion to damaged and inflamed heart valves.\u0026quot; European Heart Journal \u003cstrong\u003e40\u003c/strong\u003e(39): 3248-3259.\u003c/li\u003e\n\u003cli\u003eLiesenborghs, L., et al. (2020). \u0026quot;Coagulation: At the heart of infective endocarditis.\u0026quot; Journal of Thrombosis and Haemostasis \u003cstrong\u003e18\u003c/strong\u003e(5): 995-1008.\u003c/li\u003e\n\u003cli\u003eLuehr, M., et al. (2020). \u0026quot;Incidence and surgical outcomes of patients with native and prosthetic aortic valve endocarditis.\u0026quot; Ann Thorac Surg \u003cstrong\u003e110\u003c/strong\u003e(1): 93-101.\u003c/li\u003e\n\u003cli\u003eMaurer, G. (2006). \u0026quot;Aortic regurgitation.\u0026quot; Heart \u003cstrong\u003e92\u003c/strong\u003e(7): 994-1000.\u003c/li\u003e\n\u003cli\u003eMcDevitt, D., et al. (1995). \u0026quot;Identification of the ligand‐binding domain of the surface‐located fibrinogen receptor (clumping factor) of Staphylococcus aureus.\u0026quot; Molecular microbiology \u003cstrong\u003e16\u003c/strong\u003e(5): 895-907.\u003c/li\u003e\n\u003cli\u003eMeyers, S., et al. (2018). The differential role of platelets and fibrin in adhesion on inflamed and damaged valves in a new mouse model of early staphylococcus aureus endocarditis. European Congress on Thrombosis and Haemostasis (ECTH), Location: Marseille, France.\u003c/li\u003e\n\u003cli\u003eNappi, F., et al. (2022). \u0026quot;Infective endocarditis in high-income countries.\u0026quot; Metabolites \u003cstrong\u003e12\u003c/strong\u003e(8): 682.\u003c/li\u003e\n\u003cli\u003eNiepmann, S. T., et al. (2019). \u0026quot;Graded murine wire-induced aortic valve stenosis model mimics human functional and morphological disease phenotype.\u0026quot; Clinical Research in Cardiology \u003cstrong\u003e108\u003c/strong\u003e(8): 847-856.\u003c/li\u003e\n\u003cli\u003eOtto, C. M. and B. Prendergast (2014). \u0026quot;Aortic-valve stenosis\u0026mdash;from patients at risk to severe valve obstruction.\u0026quot; New England Journal of Medicine \u003cstrong\u003e371\u003c/strong\u003e(8): 744-756.\u003c/li\u003e\n\u003cli\u003eProctor, R. A., et al. (2006). \u0026quot;Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections.\u0026quot; Nature Reviews Microbiology \u003cstrong\u003e4\u003c/strong\u003e(4): 295-305.\u003c/li\u003e\n\u003cli\u003eRing, J., et al. (2014). \u0026quot;MRI visualization of Staphyloccocus aureus-induced infective endocarditis in mice.\u0026quot; PLoS One \u003cstrong\u003e9\u003c/strong\u003e(9): e107179.\u003c/li\u003e\n\u003cli\u003eSchwarz, C., et al. (2020). \u0026quot;Isolating crucial steps in induction of infective endocarditis with preclinical modeling of host pathogen interaction.\u0026quot; Frontiers in Microbiology \u003cstrong\u003e11\u003c/strong\u003e: 1325.\u003c/li\u003e\n\u003cli\u003eTackling, G. and V. Lala (2019). \u0026quot;Endocarditis antibiotic regimens.\u0026quot;\u003c/li\u003e\n\u003cli\u003eVahanian, A., et al. (2022). \u0026quot;2021 ESC/EACTS Guidelines for the management of valvular heart disease: developed by the Task Force for the management of valvular heart disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).\u0026quot; European Heart Journal \u003cstrong\u003e43\u003c/strong\u003e(7): 561-632.\u003c/li\u003e\n\u003cli\u003evan den Brink, F. S., et al. (2017). \u0026quot;Increased incidence of infective endocarditis after the 2009 European Society of Cardiology guideline update: a nationwide study in the Netherlands.\u0026quot; European Heart Journal-Quality of Care and Clinical Outcomes \u003cstrong\u003e3\u003c/strong\u003e(2): 141-147.\u003c/li\u003e\n\u003cli\u003eWerdan, K., et al. (2014). \u0026quot;Mechanisms of infective endocarditis: pathogen\u0026ndash;host interaction and risk states.\u0026quot; Nature Reviews Cardiology \u003cstrong\u003e11\u003c/strong\u003e(1): 35-50.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Infective Endocarditis, Staphylococcus aureus, aortic stenosis","lastPublishedDoi":"10.21203/rs.3.rs-4313097/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4313097/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIncidence of Infective endocarditis (IE) and its mortality rate despite optimal medical therapy remain high. Early diagnosis and treatment initiation are challenging because the involved immunological processes are poorly understood due to a lack of suitable \u003cem\u003ein vivo\u003c/em\u003e models and their difference to human pathophysiology.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eTo establish a novel reproducible murine IE model, based on wire injury (WI) induced endothelial damage.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eIE was established by inducing endothelial damage via wire injury followed by bacterial challenge with S. aureus using 10\u003csup\u003e4–6\u003c/sup\u003e colony-forming units (CFU). Cross-sections of valvular leaflets were prepared for scanning electron microscopy (SEM) and immunofluorescence microscopy to visualize valvular invasion of macrophages, neutrophils, and S. aureus. Bacterial cultivation was carried out from blood and valve samples.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eWire injury induced endothelial damage was observed in all mice after wire-injury in SEM imaging. We reliably induced IE using 10\u003csup\u003e5\u003c/sup\u003e (85%) and 10\u003csup\u003e6\u003c/sup\u003e (91%) CFU S. aureus after wire injury. We found significant neutrophilia in the blood and increased valvular immune cell and bacterial accumulations in IE mice.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eOur model allows for reliable IE induction and analysis of bacterial vegetation and immune cell infiltration \u003cem\u003ein vivo\u003c/em\u003e and \u003cem\u003eex vivo\u003c/em\u003e. Valvular immune cell infiltration was similar to human pathophysiology.\u003c/p\u003e","manuscriptTitle":"A novel murine model of infective endocarditis mimics human pathophysiology","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-26 02:08:08","doi":"10.21203/rs.3.rs-4313097/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"208fd34f-5c0b-482d-a785-0b77f3f5a553","owner":[],"postedDate":"April 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":31063558,"name":"Cardiac \u0026 Cardiovascular Systems"}],"tags":[],"updatedAt":"2025-04-15T14:28:35+00:00","versionOfRecord":{"articleIdentity":"rs-4313097","link":"https://doi.org/10.1371/journal.pone.0318955","journal":{"identity":"plos-one","isVorOnly":true,"title":"PLOS ONE"},"publishedOn":"2025-04-07 00:00:00","publishedOnDateReadable":"April 7th, 2025"},"versionCreatedAt":"2024-04-26 02:08:08","video":"","vorDoi":"10.1371/journal.pone.0318955","vorDoiUrl":"https://doi.org/10.1371/journal.pone.0318955","workflowStages":[]},"version":"v1","identity":"rs-4313097","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4313097","identity":"rs-4313097","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}