Aureobasidium melanogenum fungemia in a patient with nephrotic syndrome | 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 Article Aureobasidium melanogenum fungemia in a patient with nephrotic syndrome Hui Xu, Jiaxi Huang, Shengyu Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6847766/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aureobasidium melanogenum , a member of the Aureobasidium genus, is a yeast-like fungus that is widely distributed in natural environments. This organism demonstrates remarkable ecological adaptability, allowing it to thrive under extreme conditions such as high acidity, osmotic pressure, and nutrient scarcity. Aureobasidium spp . is recognized as a rare opportunistic pathogenic fungus capable of causing various clinical manifestations including mycosis, skin infections, peritonitis, and meningitis. The morphology of Aureobasidium spp . initially presents in a yeast-like form before transitioning into a mycelial form to facilitate nutrient acquisition. Due to its "dual morphology," this fungus is often misidentified as other fungal species. In this article, we present a case of nephrotic syndrome complicated by an infection with Aureobasidium melanogenum and review previous case reports to enhance the clinical understanding of this pathogen. Health sciences/Diseases Health sciences/Nephrology Aureobasidium melanogenum nephrotic syndrome infection Introduction Aureobasidium spp . is a yeast-like fungus that is widely distributed in natural environments and exhibits remarkable resilience under extreme conditions, including acidic environments, high osmotic pressure, and nutrient scarcity. This organism demonstrates significant ecological adaptability 1,2 . Since 2014, A ureobasidium has been reclassified into four distinct species: A. pullulans , A. melanigenum , A. subglaciale , and A. nambiae . According to data from the National Center for Microbial Science (2025) ( https://nmdc.cn/ ), over 60 species of Aureobasidium have been documented; the majority of these are identified as Aureobasidium pullulans . Aureobasidium is ubiquitous and can be isolated from various sources such as air, water bodies, soil, wood, other plant materials, and inorganic substances like rocks and marble. Furthermore, it possesses the capacity to produce numerous industrial products including Pullulan, β-glucan, malic acid, melanin, and surfactants 3 . Pullulan has emerged as an essential raw material in pharmaceutical applications as well as in the cosmetics and food industries due to its biodegradability, biocompatibility, water solubility، and non-toxicity 4 . Infections attributed to Aureobasidium spp . are infrequently reported; most previous case studies have primarily involved A ureobasidium pullulans with even fewer instances concerning infections caused by Aureobasidium melanogenum . In this report we present a case of infection caused by A. melanigenum that was associated with nephrotic syndrome and acute renal injury. Case report A 17-year-old male was admitted to the hospital with facial, abdominal, and bilateral lower extremity edema persisting for five days, accompanied by a high fever. His clinical presentation included edema in multiple body regions, particularly in the lower legs; however, no clear etiology for the swelling could be identified. Urinalysis revealed a significant level of albuminuria(urine protein 3+), while plasma albumin was measured at 12.3 g/L and creatinine levels were 70.5 µmol/L. Additionally, his highest recorded body temperature reached 38.8°C. CT examination of the thorax and abdomen indicated substantial fluid accumulation within both cavities, while ultrasonography demonstrated perihepatic, perisplenic, and abdominopelvic effusions. The results from clinical laboratory tests were as follows: C-reactive protein at 23.58 mg/L; D-dimer at 11.66 µg/mL; potassium (K+) at 3.44 mmol/L; sodium (Na+) at 125.71 mmol/L; calcium (Ca2+) at 1.41 mmol/L; total protein at 37 g/L; albumin at 15 g/L; white blood cell count of 9.25×10^9/L with neutrophils constituting approximately 80.9%; and a total urinary protein excretion over twenty-four hours measuring at 10.3 g. Two days following the initiation of cephalosporin therapy, the patient's temperature normalized prompting physicians to commence an intravenous infusion of methylprednisolone(40 mg/d) aimed at treating nephrotic syndrome in this patient cohort. However, only one dose of methylprednisolone was administered before he exhibited febrile symptoms again later that same day with a recorded fever reaching up to 38°C. In response to this development, glucocorticoid therapy was promptly discontinued and subsequent blood plasma metagenomics next-generation sequencing(mNGS) revealed an infection caused by Aureobasidium melanogenum (reads:232). Notably, other laboratory investigations—including antinuclear antibody profiles, vasculitis antibody profiles, tumor markers such as alpha-fetoprotein levels alongside serum tests for (1–3)-β-D-glucan and galactomannan antigen—along with respiratory infection pathogen assessments yielded negative results across all parameters tested. At the same time, the Mycobacterium tuberculosis enzyme-linked immunospot test returned positive; however, the patient exhibited no clinical signs of tuberculosis and was subsequently diagnosed with latent Mycobacterium tuberculosis infection. Due to a lack of familiarity with A. melanigenum , physicians initially misidentified it as Aspergillus niger , which is known to produce black substances. However, after consulting relevant literature, a pharmacist suggested that A. melanigenum belongs to the Aureobasidium species. Upon reviewing pertinent studies, the pharmacist recommended oral treatment with voriconazole. On the fifth day of admission, treatment commenced with 400 mg of voriconazole administered orally twice daily; this dosage was later adjusted to 200 mg per dose twice daily. On the sixth day of hospitalization, despite still experiencing transient fever—with a maximum body temperature reaching 38°C—the patient showed no further symptoms from the seventh day onward. Due to significant edema resulting from hypoproteinemia, intravenous albumin therapy was initiated alongside continuous high-dose diuretic administration(torasemide at 100 mg/day). By the eighth day post-admission, mNGS results suggestive of A. melanigenum turned negative for this patient. However, on the ninth day, serum creatinine levels rose sharply from 70.5 µmol/L to 183 µmol/L indicative of acute kidney injury; concurrently, treatment for nephrotic syndrome with methylprednisolone continued along with preventive isoniazid usage. Despite negative indications for A. melanigenum in subsequent tests, voriconazole therapy persisted until discharge from hospital care. At discharge timepoint: serum creatinine had decreased to 63.2 µmol/L; albumin levels were recorded at 27.9 g/L; C-reactive protein had diminished to 3.05 mg/L; and voriconazole blood concentration measured at 1.17 mg/L. We observed that amphotericin B was utilized in the majority of cases involving Aureobasidium spp . infections; however, in this particular case, the patient's serum creatinine levels continued to rise, indicating a state of acute renal injury. Consequently, amphotericin B exhibited greater nephrotoxicity compared to voriconazole. Furthermore, the patient presented with severe edema, and administering an intravenous infusion of amphotericin B would likely have exacerbated fluid retention in the body, worsening the edematous condition. As a result, voriconazole was ultimately selected for the treatment regimen. The duration of therapy extended over ten days, leading to a successful resolution of the infection and subsequent discharge from the hospital. One month post-discharge, we conducted a follow-up phone call with the patient. Clinical laboratory results indicated that his blood albumin had returned to 39 g/L, with 24-hour urine protein levels measuring < 150 mg/L and C-reactive protein levels at < 0.5 mg/L. Notably, he reported no symptoms indicative of fever or infection during this period. When queried about potential sources of infection upon admission, the patient stated that he had not been exposed to any damp or moldy objects or environments prior to hospitalization; rather, fever symptoms manifested only after his admission into the hospital. Literature review We conducted a comprehensive review of all case reports concerning infections attributed to Aureobasidium spp . from 1986 to the present, excluding duplicates. This search yielded a total of 47 case reports(including the current case), encompassing 49 patients. The majority of these infections were caused by A. pullulans , which accounted for 38 cases, while only nine cases were associated with A. melanigenum , as detailed in Table 1 . Specifically, among the infections linked to A. melanigenum , there were six instances of fungemia, one skin infection, one disseminated infection, and one meningitis infection; two patients succumbed to their illness. Notably, aside from the skin infection and the current patient under discussion, seven out of the nine patients had undergone catheterization and presented with immunocompromised conditions. Table 1 Summary of cases of Aureobasidium melanogenum infection Year (reference) States Age (y/o)/gender risk factor clinical performance therapeutic drug treatments Detection Methods therapeutic effect 2003 35 Italy 28/male wreck Disseminated infections Fluconazole 4 weeks Blood cultures, microscopic observation Improve 2011 16 USA 11/male intestinal lymphangiectasia, protein losing enteropathy, lymphopenia presented fungemia Amphotericin B 2 weeks DNA sequencing Improve 2016 37 China, Taiwan 46/male No risk Skin infections Itraconazole 3 weeks DNA sequencing Improve 2018 6 China, Taiwan 2/male Acute myeloid leukemia (M5b) fungemia Caspofungin 3 weeks DNA sequencing Improve 2021 25 Brazilian 22/male ulcerative colitis and HIV meningitis Amphotericin B 2 weeks DNA sequencing Improve 2022 7 Japan 20/male central venous catheter fungemia Micafungin amphotericin B Not mention DNA sequencing Improve 2022 26 India 0/female low birth weight 、 premature baby fungemia Fluconazole amphotericin B 4 day DNA sequencing Death 2022 20 USA 60/male heart failure 、 PICC Fungemia Caspofungin posaconazole 2 weeks MALDI-TOFF Death Discussion The genus Aureobasidium belongs to the order Dothideales ( Ascomycota , Dothideomycetes ) and is characterized as a dimorphic fungus exhibiting both a primary yeast-like form and a secondary filamentous form. This genus is widely distributed globally and is commonly referred to as "black yeast" due to its capacity for melanin synthesis 2 . A distinguishing feature of Aureobasidium spp . is their morphological transformation, initially resembling Candida species by appearing as yeast-like cells. The colonies typically start off white, yellow, or rose-cream in color before transitioning to black or dark green with fibrous characteristics, producing black filamentous colonies within approximately 1–2 weeks. Consequently, they are often misidentified at first glance as Candida 5–7 , Cryptococcus 8 , or Aspergillus niger . Most patients documented in previous case reports of Aureobasidium spp . infections had experienced catheter implantation procedures such as peritoneal dialysis catheterization 9–13 , parenteral nutrition catheters 5,14–16 , and central venous catheters 6,15,17–20 , additionally, many were treated with immunosuppressive drugs or presented with immunocompromised states themselves 7,8,21–28 , or were treated with chemotherapeutic drugs 29–31 , Some patients had undergone ocular-related surgeries or manipulations 32–34 , or had a history of trauma 35,36 , notably, six cases reported no identifiable risk factors associated with infection 37–40 . Aureobasidium spp . infections can affect multiple systems throughout the body and present with nonspecific clinical symptoms including fungemia; skin infections; pulmonary infections; disseminated infections; meningitis; keratitis; peritonitis; localized abscesses; and lymphadenitis. Wang, M et al 41 suggest that Aureobasidium melanogenum exhibits a higher frequency of opportunistic infections compared to A. pullulans . They assessed the thermotolerance of two genera within Aureobasidium spp . by comparing the colony diameters of two species cultured on different media at temperatures of 24°C and 37°C, utilizing a total of 92 strains—45 strains identified as A. pullulans and 47 as A. melanogenum . In terms of melanisation, it was observed that A. melanogenum demonstrated superior melanisation at 37°C not only compared to its own growth at 24°C but also in relation to A. pullulans under identical temperature conditions (although no significant difference was noted between the two species at 24°C). In general, growth at body temperature is a prerequisite for fungal pathogens to survive within mammalian hosts 42 . It is evident that A. melanogenum has a greater capacity for growth in humans than does A. pullulans , thereby increasing the likelihood of opportunistic infections occurring. Several virulence factors associated with A. melanogenum have been investigated by Černoša et al 43 , which include its ability to grow at human body temperature, production of iron carriers, hemolytic activity, and absorption capabilities for various human neurotransmitters. The findings indicated that nearly all strains of A. melanogenum exhibited enhanced growth compared to other Aureobasidium genera when incubated at 37°C. In addition, A. melanigenum was found to produce iron carriers at 37°C. Notably, there were variations in the quantity of iron carriers produced; however, all tested strains of A. melanigenum possessed at least one homologue of the SidC and SidD proteins, which are implicated in the acquisition of iron via these carriers. Furthermore, a significant majority of short-stemmed mold strains exhibited α-hemolysis. Najafzadeh et al 44 investigated 104 strains of A. pullulans and A. melanigenum isolated from clinical and environmental samples, revealing that A. melanigenum appeared significantly more frequently than A. pullulans among the 51 clinical strains (84%[43/51] versus 16%[8/51]). Additionally, A. melanigenum was more prevalent in clinical samples overall. Moreover, within both species' colonies, the coloration varied: colonies of A. pullulans ranged from off-white to pink, creamy white to dark brown, and occasionally black; conversely, colonies of A. melanigenum were predominantly milky white but could change to black over time 44 . Among the 47 case reports retrieved (including this study), there were 36 instances documenting infections caused by A. pullulans compared to only nine reports involving A. melanigenum and two concerning other Aureobasidium species. Given that distinguishing between A. melanigenum and A. pullulans is challenging due to their similarities, it is plausible that many infections attributed to A. pullulans may actually be caused by misidentified cases of A. melanigenum . Since infections caused by Aureobasidium spp . are rarely reported and there is no established standard of treatment, only eleven previous cases have been documented with drug sensitivity tests, as illustrated in Table 2 . From this table, it is evident that Aureobasidium spp . exhibited resistance to fluconazole in nearly all reported cases, while demonstrating sensitivity to Amphotericin B, Voriconazole, Itraconazole, and Posaconazole. In fact, Najafzadeh et al 44 conducted a comparative study on the in vitro activity of eight antifungal agents against 104 strains of Aureobasidium spp . revealing that 95% of these strains were resistant to fluconazole (MIC ≤ 64 µg/ml). This finding aligns with the results from prior case reports regarding in vitro drug susceptibility testing. Furthermore, they found that 95% of the Aureobasidium spp . strains were sensitive to Amphotericin B (MIC: 1 µg/ml), Posaconazole (MIC: 0.5 µg/ml), and Itraconazole (MIC: 0.5 µg/ml). Notably, fluconazole exhibited the highest average MIC at 52.75 µg/ml; conversely, Voriconazole, Amphotericin B, Micafungin, Itraconazole, and Posaconazole demonstrated significantly lower mean MIC. Table 2 Results of relevant drug sensitivity tests in 11 case reports Year (reference) Infection Symptoms (fungus) Antifungal susceptibility in vitro: MIC (Units for: ug/ml) 2005 18 Fungemia(A. pullulans) Itraconazole:0.03; Ketoconazole:0.03; Flucytosine:0.5; Amphotericin B:0.5; Fluconazole:4 2012 45 Nail-detachment(A. pullulans) Itraconazole:0.25; Posaconazole:0.032; Amphotericin B:0.5; Amorolfine:1; Terbinafine:1; Ketoconazole:2; Caspofungin:32; Flucytosine:32; Voriconazole:32; Fluconazole:64 2012 38 Meningitis(A. proteae) Voriconazole:0.03; Amphotericin B:0.06 2016 37 Skin infections(A.melanigenum) 1st: Itraconazole:0.25; Voriconazole:0.125; Terbinafine:0.5; Amphotericin B:1; griseofulvin:16 2nd: Itraconazole:0.25; Voriconazole:0.06; Terbinafine:0.5; Amphotericin B:0.5; griseofulvin: 16 2017 5 Fungemia(A.pullulans) Amphotericin B:1; Caspofungin:1; Micafungin:2; Triazole:>16 2018 8 subcutaneous cyst(A. pullulans) Itraconazole:0.03; Amphotericin B:0.5; Voriconazole:0.5; Caspofungin:4; Fluconazole:4 2018 6 Fungemia(A.melanigenum) Voriconazole:0.03; Amphotericin B:0.125; Anidulafungin:0.125; Flucytosine:4 2018 46 Fungemia(A. pullulans) Caspofungin:<0.015; Posaconazole:0.015; Amphotericin B:0.12; Voriconazole:0.12; Micafungin:0.25; Fluconazole:8 2022 7 Fungemia(A.melanigenum) Voriconazole:0.03; Itraconazole:0.06; Micafungin:0.25; Flucytosine:0.25; Caspofungin:0.5; Amphotericin B:1; Fluconazole:8 2022 26 Fungemia(A.melanigenum) Voriconazole:0.125; Itraconazole:0.25; Caspofungin:0.25; Amphotericin B:0.5; Flucytosine:32 2022 20 Fungemia(A. pullulans) 1st: Posaconazole:0.06; Voriconazole:0.06; Caspofungin:>8; Fluconazole:16 2nd: Voriconazole:0.125; Posaconazole:0.25; Amphotericin B:0.5; Terbinafine:1; Isavuconazole:4; Caspofungin:>8; Fluconazole:32; In summary, we present a case of nephrotic syndrome associated with an infection caused by Aureobasidium melanigenum . The patient had no history of catheter placement and lacked any significant past medical history or genetic risk factors. Due to the nephrotic syndrome, he was admitted to the hospital exhibiting hypoproteinemia, severe edema, and electrolyte imbalances. These conditions contributed to his temporary immunocompromised state and subsequent infection by this rare opportunistic pathogen. Considering his pronounced edema and acute kidney injury status, we opted for treatment with voriconazole based on our prior experience documented in previous case reports. Historically, misunderstandings regarding Aureobasidium spp . have arisen due to limitations in testing technology and insufficient knowledge about these organisms. Despite the rapid advancements in diagnostic techniques today, there remains a pressing need to enhance awareness and understanding of Aureobasidium spp . Declarations Ethical approval The study was approved by the Institutional Review Board of First Affiliated Hospital of USTC (No.2023-RE-146). All subjects provided informed consent according to ethical guidelines for academic research, and all experiments were performed in accordance with the relevant guidelines and regulations. Acknowledgements The author expresses gratitude to all the physicians in the Department of Nephrology at the First Affiliated Hospital of USTC (Anhui Provincial Hospital) for their invaluable guidance regarding the treatment plan for this case. Author contributions Hui Xu and Jiaxi Huang were responsible for the organization of case data and the composition of the manuscript, while Shengyu zhang provided guidance during the revision process and offered support for funding. Competing interests The authors declare no competing interests. Data availability The datasets generated and/or analyzed during the current study are available upon reasonable request to the corresponding author. Footnotes Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. These authors contributed equally: Hui Xu and Jiaxi Huang References Gostincar, C. et al. Genome sequencing of four Aureobasidium pullulans varieties: biotechnological potential, stress tolerance, and description of new species. BMC GENOMICS 15 549. (2014). https://doi.org/10.1186/1471-2164-15-549 Xiao, D. et al. Advances in Aureobasidium research: Paving the path to industrial utilization. MICROB BIOTECHNOL 17 e14535. (2024). https://doi.org/10.1111/1751-7915.14535 Rensink, S., van Nieuwenhuijzen, E. J., Sailer, M. F., Struck, C. & Wösten, H. A. B. Use of Aureobasidium in a sustainable economy. APPL MICROBIOL BIOT 108 202. 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Fungi between extremo tolerance and opportunistic pathogenicity on humans. FUNGAL DIVERS 93 195. (2018). https://doi.org/10.1007/s13225-018-0414-8 Černoša, A. Virulence Traits and Population Genomics of the Black Yeast Aureobasidium melanogenum . J. Fungi (Basel) . 8665. https://doi.org/10.3390/jof7080665 (2021). Najafzadeh, M. J. S. D. K. M., In vitro activities of eight antifungal drugs against 104 environmental and clinical isolates of Aureobasidium pullulans . Antimicrob Agents Chemother. 9 5629. (2014). https://doi.org/10.1128/AAC.03095-14 Arabatzis, M. Hypothyroidism-related onycholysis with Aureobasidium pullulans colonization successfully treated with antifungal therapy. CLIN EXP DERMATOL 37 370. (2012). https://doi.org/10.1111/j.1365-2230.2012.04347.x Mittal, J., Jmmcr, E. P. M. D. & S. W. P. L. & Fungemia caused by Aureobasidium pullulans in a patient with advanced AIDS: a case report and review of the medical literature. JMM Case Rep. JMM Case Rep. e005144. https://doi.org/10.1099/jmmcr.0.005144 (2018). 4. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6847766","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":475774371,"identity":"da1496ca-dbc7-4762-ae81-5786068afc3f","order_by":0,"name":"Hui Xu","email":"","orcid":"","institution":"Xuancheng People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Xu","suffix":""},{"id":475774372,"identity":"9c75c4c4-de51-4aac-92a1-23a9ce35175f","order_by":1,"name":"Jiaxi Huang","email":"","orcid":"","institution":"Huoqiu County First People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jiaxi","middleName":"","lastName":"Huang","suffix":""},{"id":475774373,"identity":"c2682226-2df0-4e89-8d4b-68c6441a5b31","order_by":2,"name":"Shengyu Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYBACNobz339I/rOp75c/fIA4LXyMBwwkLNjSGGfOYEsgToscM1BLBdthxg03eAyIdBjbgQSDGzyHmQ1u93y88YbBTk63gZAWngMHEmdIpLNJ3jm72XIOQ7Kx2QFCWiQONhyWMLDm4TuQu02ah+FA4jaCWuQfMzb/SWCWYDiQ84xILQzHmBkkDjgbCNzIYSNWyxk2BsmGtATJnmPGlnMMiPCLfANYi00CP3vzwxtvKuzkCGpBARLERg2yFlJ1jIJRMApGwYgAAD4iQnys71AyAAAAAElFTkSuQmCC","orcid":"","institution":"the First Affiliated Hospital of USTC (Anhui Provincial Hospital)","correspondingAuthor":true,"prefix":"","firstName":"Shengyu","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-06-08 13:38:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6847766/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6847766/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":93706355,"identity":"175ea0a9-1f1b-4b27-b41f-f57e4bea6150","added_by":"auto","created_at":"2025-10-16 16:38:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":521817,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6847766/v1/3a38f22c-1a07-4599-8a9b-85d9163b1f52.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Aureobasidium melanogenum fungemia in a patient with nephrotic syndrome","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cem\u003eAureobasidium spp\u003c/em\u003e. is a yeast-like fungus that is widely distributed in natural environments and exhibits remarkable resilience under extreme conditions, including acidic environments, high osmotic pressure, and nutrient scarcity. This organism demonstrates significant ecological adaptability\u003csup\u003e1,2\u003c/sup\u003e. Since 2014, A\u003cem\u003eureobasidium\u003c/em\u003e has been reclassified into four distinct species: \u003cem\u003eA. pullulans\u003c/em\u003e, \u003cem\u003eA. melanigenum\u003c/em\u003e, \u003cem\u003eA. subglaciale\u003c/em\u003e, and \u003cem\u003eA. nambiae\u003c/em\u003e. According to data from the National Center for Microbial Science (2025) (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://nmdc.cn/\u003c/span\u003e\u003cspan address=\"https://nmdc.cn/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), over 60 species of \u003cem\u003eAureobasidium\u003c/em\u003e have been documented; the majority of these are identified as \u003cem\u003eAureobasidium pullulans\u003c/em\u003e. \u003cem\u003eAureobasidium\u003c/em\u003e is ubiquitous and can be isolated from various sources such as air, water bodies, soil, wood, other plant materials, and inorganic substances like rocks and marble. Furthermore, it possesses the capacity to produce numerous industrial products including Pullulan, β-glucan, malic acid, melanin, and surfactants\u003csup\u003e3\u003c/sup\u003e. Pullulan has emerged as an essential raw material in pharmaceutical applications as well as in the cosmetics and food industries due to its biodegradability, biocompatibility, water solubility، and non-toxicity\u003csup\u003e4\u003c/sup\u003e. Infections attributed to \u003cem\u003eAureobasidium spp\u003c/em\u003e. are infrequently reported; most previous case studies have primarily involved A\u003cem\u003eureobasidium pullulans\u003c/em\u003e with even fewer instances concerning infections caused by \u003cem\u003eAureobasidium melanogenum\u003c/em\u003e. In this report we present a case of infection caused by \u003cem\u003eA. melanigenum\u003c/em\u003e that was associated with nephrotic syndrome and acute renal injury.\u003c/p\u003e "},{"header":"Case report","content":"\u003cp\u003eA 17-year-old male was admitted to the hospital with facial, abdominal, and bilateral lower extremity edema persisting for five days, accompanied by a high fever. His clinical presentation included edema in multiple body regions, particularly in the lower legs; however, no clear etiology for the swelling could be identified. Urinalysis revealed a significant level of albuminuria(urine protein 3+), while plasma albumin was measured at 12.3 g/L and creatinine levels were 70.5 µmol/L. Additionally, his highest recorded body temperature reached 38.8°C. CT examination of the thorax and abdomen indicated substantial fluid accumulation within both cavities, while ultrasonography demonstrated perihepatic, perisplenic, and abdominopelvic effusions. The results from clinical laboratory tests were as follows: C-reactive protein at 23.58 mg/L; D-dimer at 11.66 µg/mL; potassium (K+) at 3.44 mmol/L; sodium (Na+) at 125.71 mmol/L; calcium (Ca2+) at 1.41 mmol/L; total protein at 37 g/L; albumin at 15 g/L; white blood cell count of 9.25×10^9/L with neutrophils constituting approximately 80.9%; and a total urinary protein excretion over twenty-four hours measuring at 10.3 g. Two days following the initiation of cephalosporin therapy, the patient's temperature normalized prompting physicians to commence an intravenous infusion of methylprednisolone(40 mg/d) aimed at treating nephrotic syndrome in this patient cohort. However, only one dose of methylprednisolone was administered before he exhibited febrile symptoms again later that same day with a recorded fever reaching up to 38°C. In response to this development, glucocorticoid therapy was promptly discontinued and subsequent blood plasma metagenomics next-generation sequencing(mNGS) revealed an infection caused by \u003cem\u003eAureobasidium melanogenum\u003c/em\u003e(reads:232). Notably, other laboratory investigations—including antinuclear antibody profiles, vasculitis antibody profiles, tumor markers such as alpha-fetoprotein levels alongside serum tests for (1–3)-β-D-glucan and galactomannan antigen—along with respiratory infection pathogen assessments yielded negative results across all parameters tested. At the same time, the Mycobacterium tuberculosis enzyme-linked immunospot test returned positive; however, the patient exhibited no clinical signs of tuberculosis and was subsequently diagnosed with latent Mycobacterium tuberculosis infection. Due to a lack of familiarity with \u003cem\u003eA. melanigenum\u003c/em\u003e, physicians initially misidentified it as \u003cem\u003eAspergillus niger\u003c/em\u003e, which is known to produce black substances. However, after consulting relevant literature, a pharmacist suggested that \u003cem\u003eA. melanigenum\u003c/em\u003e belongs to the \u003cem\u003eAureobasidium\u003c/em\u003e species. Upon reviewing pertinent studies, the pharmacist recommended oral treatment with voriconazole. On the fifth day of admission, treatment commenced with 400 mg of voriconazole administered orally twice daily; this dosage was later adjusted to 200 mg per dose twice daily. On the sixth day of hospitalization, despite still experiencing transient fever—with a maximum body temperature reaching 38°C—the patient showed no further symptoms from the seventh day onward. Due to significant edema resulting from hypoproteinemia, intravenous albumin therapy was initiated alongside continuous high-dose diuretic administration(torasemide at 100 mg/day). By the eighth day post-admission, mNGS results suggestive of \u003cem\u003eA. melanigenum\u003c/em\u003e turned negative for this patient. However, on the ninth day, serum creatinine levels rose sharply from 70.5 µmol/L to 183 µmol/L indicative of acute kidney injury; concurrently, treatment for nephrotic syndrome with methylprednisolone continued along with preventive isoniazid usage. Despite negative indications for \u003cem\u003eA. melanigenum\u003c/em\u003e in subsequent tests, voriconazole therapy persisted until discharge from hospital care. At discharge timepoint: serum creatinine had decreased to 63.2 µmol/L; albumin levels were recorded at 27.9 g/L; C-reactive protein had diminished to 3.05 mg/L; and voriconazole blood concentration measured at 1.17 mg/L.\u003c/p\u003e\u003cp\u003eWe observed that amphotericin B was utilized in the majority of cases involving \u003cem\u003eAureobasidium spp\u003c/em\u003e. infections; however, in this particular case, the patient's serum creatinine levels continued to rise, indicating a state of acute renal injury. Consequently, amphotericin B exhibited greater nephrotoxicity compared to voriconazole. Furthermore, the patient presented with severe edema, and administering an intravenous infusion of amphotericin B would likely have exacerbated fluid retention in the body, worsening the edematous condition. As a result, voriconazole was ultimately selected for the treatment regimen. The duration of therapy extended over ten days, leading to a successful resolution of the infection and subsequent discharge from the hospital. One month post-discharge, we conducted a follow-up phone call with the patient. Clinical laboratory results indicated that his blood albumin had returned to 39 g/L, with 24-hour urine protein levels measuring \u0026lt; 150 mg/L and C-reactive protein levels at \u0026lt; 0.5 mg/L. Notably, he reported no symptoms indicative of fever or infection during this period. When queried about potential sources of infection upon admission, the patient stated that he had not been exposed to any damp or moldy objects or environments prior to hospitalization; rather, fever symptoms manifested only after his admission into the hospital.\u003c/p\u003e\u003cp\u003eLiterature review\u003c/p\u003e\u003cp\u003eWe conducted a comprehensive review of all case reports concerning infections attributed to \u003cem\u003eAureobasidium spp\u003c/em\u003e. from 1986 to the present, excluding duplicates. This search yielded a total of 47 case reports(including the current case), encompassing 49 patients. The majority of these infections were caused by \u003cem\u003eA. pullulans\u003c/em\u003e, which accounted for 38 cases, while only nine cases were associated with \u003cem\u003eA. melanigenum\u003c/em\u003e, as detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Specifically, among the infections linked to \u003cem\u003eA. melanigenum\u003c/em\u003e, there were six instances of fungemia, one skin infection, one disseminated infection, and one meningitis infection; two patients succumbed to their illness. Notably, aside from the skin infection and the current patient under discussion, seven out of the nine patients had undergone catheterization and presented with immunocompromised conditions.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of cases of \u003cem\u003eAureobasidium melanogenum\u003c/em\u003e infection\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYear (reference)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStates\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eAge (y/o)/gender\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003erisk factor\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eclinical performance\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003etherapeutic drug\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003etreatments\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDetection Methods\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003etherapeutic effect\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2003\u003csup\u003e35\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28/male\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ewreck\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDisseminated infections\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFluconazole\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4 weeks\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBlood cultures, microscopic observation\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImprove\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2011\u003csup\u003e16\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11/male\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eintestinal lymphangiectasia, protein losing enteropathy, lymphopenia presented\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003efungemia\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAmphotericin B\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 weeks\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDNA\u003c/p\u003e \u003cp\u003esequencing\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImprove\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2016\u003csup\u003e37\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eChina, Taiwan\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46/male\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo risk\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSkin infections\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eItraconazole\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 weeks\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDNA\u003c/p\u003e \u003cp\u003esequencing\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImprove\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eChina, Taiwan\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/male\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAcute myeloid leukemia (M5b)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003efungemia\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCaspofungin\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 weeks\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDNA\u003c/p\u003e \u003cp\u003esequencing\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImprove\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2021\u003csup\u003e25\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBrazilian\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22/male\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eulcerative colitis and HIV\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003emeningitis\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAmphotericin B\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 weeks\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDNA\u003c/p\u003e \u003cp\u003esequencing\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImprove\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20/male\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecentral venous catheter\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003efungemia\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMicafungin amphotericin B\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNot mention\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDNA\u003c/p\u003e \u003cp\u003esequencing\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImprove\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/female\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003elow birth weight 、 premature baby\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003efungemia\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFluconazole amphotericin B\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4 day\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDNA\u003c/p\u003e \u003cp\u003esequencing\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60/male\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eheart failure 、 PICC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFungemia\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCaspofungin posaconazole\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 weeks\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMALDI-TOFF\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe genus \u003cem\u003eAureobasidium\u003c/em\u003e belongs to the order \u003cem\u003eDothideales\u003c/em\u003e (\u003cem\u003eAscomycota\u003c/em\u003e, \u003cem\u003eDothideomycetes\u003c/em\u003e) and is characterized as a dimorphic fungus exhibiting both a primary yeast-like form and a secondary filamentous form. This genus is widely distributed globally and is commonly referred to as \"black yeast\" due to its capacity for melanin synthesis\u003csup\u003e2\u003c/sup\u003e. A distinguishing feature of \u003cem\u003eAureobasidium spp\u003c/em\u003e. is their morphological transformation, initially resembling \u003cem\u003eCandida\u003c/em\u003e species by appearing as yeast-like cells. The colonies typically start off white, yellow, or rose-cream in color before transitioning to black or dark green with fibrous characteristics, producing black filamentous colonies within approximately 1\u0026ndash;2 weeks. Consequently, they are often misidentified at first glance as \u003cem\u003eCandida\u003c/em\u003e\u003csup\u003e5\u0026ndash;7\u003c/sup\u003e, \u003cem\u003eCryptococcus\u003c/em\u003e\u003csup\u003e8\u003c/sup\u003e, or \u003cem\u003eAspergillus niger\u003c/em\u003e. Most patients documented in previous case reports of \u003cem\u003eAureobasidium spp\u003c/em\u003e. infections had experienced catheter implantation procedures such as peritoneal dialysis catheterization\u003csup\u003e9\u0026ndash;13\u003c/sup\u003e, parenteral nutrition catheters\u003csup\u003e5,14\u0026ndash;16\u003c/sup\u003e, and central venous catheters\u003csup\u003e6,15,17\u0026ndash;20\u003c/sup\u003e, additionally, many were treated with immunosuppressive drugs or presented with immunocompromised states themselves\u003csup\u003e7,8,21\u0026ndash;28\u003c/sup\u003e, or were treated with chemotherapeutic drugs\u003csup\u003e29\u0026ndash;31\u003c/sup\u003e, Some patients had undergone ocular-related surgeries or manipulations\u003csup\u003e32\u0026ndash;34\u003c/sup\u003e, or had a history of trauma\u003csup\u003e35,36\u003c/sup\u003e, notably, six cases reported no identifiable risk factors associated with infection\u003csup\u003e37\u0026ndash;40\u003c/sup\u003e. \u003cem\u003eAureobasidium spp\u003c/em\u003e. infections can affect multiple systems throughout the body and present with nonspecific clinical symptoms including fungemia; skin infections; pulmonary infections; disseminated infections; meningitis; keratitis; peritonitis; localized abscesses; and lymphadenitis.\u003c/p\u003e \u003cp\u003eWang, M et al\u003csup\u003e41\u003c/sup\u003e suggest that \u003cem\u003eAureobasidium melanogenum\u003c/em\u003e exhibits a higher frequency of opportunistic infections compared to \u003cem\u003eA. pullulans\u003c/em\u003e. They assessed the thermotolerance of two genera within \u003cem\u003eAureobasidium spp\u003c/em\u003e. by comparing the colony diameters of two species cultured on different media at temperatures of 24\u0026deg;C and 37\u0026deg;C, utilizing a total of 92 strains\u0026mdash;45 strains identified as \u003cem\u003eA. pullulans\u003c/em\u003e and 47 as \u003cem\u003eA. melanogenum\u003c/em\u003e. In terms of melanisation, it was observed that \u003cem\u003eA. melanogenum\u003c/em\u003e demonstrated superior melanisation at 37\u0026deg;C not only compared to its own growth at 24\u0026deg;C but also in relation to \u003cem\u003eA. pullulans\u003c/em\u003e under identical temperature conditions (although no significant difference was noted between the two species at 24\u0026deg;C). In general, growth at body temperature is a prerequisite for fungal pathogens to survive within mammalian hosts\u003csup\u003e42\u003c/sup\u003e. It is evident that \u003cem\u003eA. melanogenum\u003c/em\u003e has a greater capacity for growth in humans than does \u003cem\u003eA. pullulans\u003c/em\u003e, thereby increasing the likelihood of opportunistic infections occurring. Several virulence factors associated with \u003cem\u003eA. melanogenum\u003c/em\u003e have been investigated by Černoša et al\u003csup\u003e43\u003c/sup\u003e, which include its ability to grow at human body temperature, production of iron carriers, hemolytic activity, and absorption capabilities for various human neurotransmitters. The findings indicated that nearly all strains of \u003cem\u003eA. melanogenum\u003c/em\u003e exhibited enhanced growth compared to other \u003cem\u003eAureobasidium\u003c/em\u003e genera when incubated at 37\u0026deg;C. In addition, \u003cem\u003eA. melanigenum\u003c/em\u003e was found to produce iron carriers at 37\u0026deg;C. Notably, there were variations in the quantity of iron carriers produced; however, all tested strains of \u003cem\u003eA. melanigenum\u003c/em\u003e possessed at least one homologue of the SidC and SidD proteins, which are implicated in the acquisition of iron via these carriers. Furthermore, a significant majority of short-stemmed mold strains exhibited α-hemolysis. Najafzadeh et al\u003csup\u003e44\u003c/sup\u003e investigated 104 strains of \u003cem\u003eA. pullulans\u003c/em\u003e and \u003cem\u003eA. melanigenum\u003c/em\u003e isolated from clinical and environmental samples, revealing that \u003cem\u003eA. melanigenum\u003c/em\u003e appeared significantly more frequently than \u003cem\u003eA. pullulans\u003c/em\u003e among the 51 clinical strains (84%[43/51] versus 16%[8/51]). Additionally, \u003cem\u003eA. melanigenum\u003c/em\u003e was more prevalent in clinical samples overall. Moreover, within both species' colonies, the coloration varied: colonies of \u003cem\u003eA. pullulans\u003c/em\u003e ranged from off-white to pink, creamy white to dark brown, and occasionally black; conversely, colonies of \u003cem\u003eA. melanigenum\u003c/em\u003e were predominantly milky white but could change to black over time\u003csup\u003e44\u003c/sup\u003e. Among the 47 case reports retrieved (including this study), there were 36 instances documenting infections caused by \u003cem\u003eA. pullulans\u003c/em\u003e compared to only nine reports involving \u003cem\u003eA. melanigenum\u003c/em\u003e and two concerning other \u003cem\u003eAureobasidium\u003c/em\u003e species. Given that distinguishing between \u003cem\u003eA. melanigenum\u003c/em\u003e and \u003cem\u003eA. pullulans\u003c/em\u003e is challenging due to their similarities, it is plausible that many infections attributed to \u003cem\u003eA. pullulans\u003c/em\u003e may actually be caused by misidentified cases of \u003cem\u003eA. melanigenum\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eSince infections caused by \u003cem\u003eAureobasidium spp\u003c/em\u003e. are rarely reported and there is no established standard of treatment, only eleven previous cases have been documented with drug sensitivity tests, as illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. From this table, it is evident that \u003cem\u003eAureobasidium spp\u003c/em\u003e. exhibited resistance to fluconazole in nearly all reported cases, while demonstrating sensitivity to Amphotericin B, Voriconazole, Itraconazole, and Posaconazole. In fact, Najafzadeh et al\u003csup\u003e44\u003c/sup\u003e conducted a comparative study on the in vitro activity of eight antifungal agents against 104 strains of \u003cem\u003eAureobasidium spp\u003c/em\u003e. revealing that 95% of these strains were resistant to fluconazole (MIC\u0026thinsp;\u0026le;\u0026thinsp;64 \u0026micro;g/ml). This finding aligns with the results from prior case reports regarding in vitro drug susceptibility testing. Furthermore, they found that 95% of the \u003cem\u003eAureobasidium spp\u003c/em\u003e. strains were sensitive to Amphotericin B (MIC: 1 \u0026micro;g/ml), Posaconazole (MIC: 0.5 \u0026micro;g/ml), and Itraconazole (MIC: 0.5 \u0026micro;g/ml). Notably, fluconazole exhibited the highest average MIC at 52.75 \u0026micro;g/ml; conversely, Voriconazole, Amphotericin B, Micafungin, Itraconazole, and Posaconazole demonstrated significantly lower mean MIC.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of relevant drug sensitivity tests in 11 case reports\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYear (reference)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInfection Symptoms (fungus)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAntifungal susceptibility in vitro: MIC (Units for: ug/ml)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2005\u003csup\u003e18\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFungemia(A. pullulans)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eItraconazole:0.03; Ketoconazole:0.03; Flucytosine:0.5; Amphotericin B:0.5; Fluconazole:4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2012\u003csup\u003e45\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNail-detachment(A. pullulans)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eItraconazole:0.25; Posaconazole:0.032; Amphotericin B:0.5; Amorolfine:1; Terbinafine:1; Ketoconazole:2; Caspofungin:32; Flucytosine:32; Voriconazole:32; Fluconazole:64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2012\u003csup\u003e38\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeningitis(A. proteae)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVoriconazole:0.03; Amphotericin B:0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2016\u003csup\u003e37\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSkin infections(A.melanigenum)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1st: Itraconazole:0.25; Voriconazole:0.125; Terbinafine:0.5; Amphotericin B:1; griseofulvin:16\u003c/p\u003e \u003cp\u003e2nd: Itraconazole:0.25; Voriconazole:0.06; Terbinafine:0.5; Amphotericin B:0.5; griseofulvin: 16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2017\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFungemia(A.pullulans)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAmphotericin B:1; Caspofungin:1; Micafungin:2; Triazole:\u0026gt;16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018\u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003esubcutaneous cyst(A. pullulans)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eItraconazole:0.03; Amphotericin B:0.5; Voriconazole:0.5; Caspofungin:4; Fluconazole:4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFungemia(A.melanigenum)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVoriconazole:0.03; Amphotericin B:0.125; Anidulafungin:0.125; Flucytosine:4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018\u003csup\u003e46\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFungemia(A. pullulans)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCaspofungin:\u0026lt;0.015; Posaconazole:0.015; Amphotericin B:0.12; Voriconazole:0.12; Micafungin:0.25; Fluconazole:8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFungemia(A.melanigenum)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVoriconazole:0.03; Itraconazole:0.06; Micafungin:0.25; Flucytosine:0.25; Caspofungin:0.5; Amphotericin B:1; Fluconazole:8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFungemia(A.melanigenum)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVoriconazole:0.125; Itraconazole:0.25; Caspofungin:0.25; Amphotericin B:0.5; Flucytosine:32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFungemia(A. pullulans)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1st: Posaconazole:0.06; Voriconazole:0.06; Caspofungin:\u0026gt;8; Fluconazole:16\u003c/p\u003e \u003cp\u003e2nd: Voriconazole:0.125; Posaconazole:0.25; Amphotericin B:0.5; Terbinafine:1; Isavuconazole:4; Caspofungin:\u0026gt;8; Fluconazole:32;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn summary, we present a case of nephrotic syndrome associated with an infection caused by \u003cem\u003eAureobasidium melanigenum\u003c/em\u003e. The patient had no history of catheter placement and lacked any significant past medical history or genetic risk factors. Due to the nephrotic syndrome, he was admitted to the hospital exhibiting hypoproteinemia, severe edema, and electrolyte imbalances. These conditions contributed to his temporary immunocompromised state and subsequent infection by this rare opportunistic pathogen. Considering his pronounced edema and acute kidney injury status, we opted for treatment with voriconazole based on our prior experience documented in previous case reports. Historically, misunderstandings regarding \u003cem\u003eAureobasidium spp\u003c/em\u003e. have arisen due to limitations in testing technology and insufficient knowledge about these organisms. Despite the rapid advancements in diagnostic techniques today, there remains a pressing need to enhance awareness and understanding of \u003cem\u003eAureobasidium spp\u003c/em\u003e.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthical approval\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Institutional Review Board of First Affiliated Hospital of USTC (No.2023-RE-146). All subjects provided informed consent according to ethical guidelines for academic research, and all experiments were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThe author expresses gratitude to all the physicians in the Department of Nephrology at the First Affiliated Hospital of USTC (Anhui Provincial Hospital) for their invaluable guidance regarding the treatment plan for this case.\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Hui Xu and Jiaxi Huang were responsible for the organization of case data and the composition of the manuscript, while Shengyu zhang provided guidance during the revision process and offered support for funding.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eData availability\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available upon reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003eFootnotes\u003c/p\u003e\n\u003cp\u003eSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\u003c/p\u003e\n\u003cp\u003eThese authors contributed equally: Hui Xu and Jiaxi Huang\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eGostincar, C. et al. 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(2014). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1128/AAC.03095-14\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eArabatzis, M. Hypothyroidism-related onycholysis with \u003cem\u003eAureobasidium pullulans\u003c/em\u003e colonization successfully treated with antifungal therapy. \u003cem\u003eCLIN EXP DERMATOL\u003c/em\u003e 37 370. (2012). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1365-2230.2012.04347.x\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMittal, J., Jmmcr, E. P. M. D. \u0026amp; S. W. P. L. \u0026amp; Fungemia caused by \u003cem\u003eAureobasidium pullulans\u003c/em\u003e in a patient with advanced AIDS: a case report and review of the medical literature. JMM Case Rep. \u003cem\u003eJMM Case Rep.\u003c/em\u003e e005144. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1099/jmmcr.0.005144\u003c/span\u003e\u003c/span\u003e (2018). 4.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"Aureobasidium melanogenum, nephrotic syndrome, infection","lastPublishedDoi":"10.21203/rs.3.rs-6847766/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6847766/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cem\u003eAureobasidium melanogenum\u003c/em\u003e, a member of the \u003cem\u003eAureobasidium\u003c/em\u003e genus, is a yeast-like fungus that is widely distributed in natural environments. This organism demonstrates remarkable ecological adaptability, allowing it to thrive under extreme conditions such as high acidity, osmotic pressure, and nutrient scarcity. \u003cem\u003eAureobasidium spp\u003c/em\u003e. is recognized as a rare opportunistic pathogenic fungus capable of causing various clinical manifestations including mycosis, skin infections, peritonitis, and meningitis. The morphology of \u003cem\u003eAureobasidium spp\u003c/em\u003e. initially presents in a yeast-like form before transitioning into a mycelial form to facilitate nutrient acquisition. Due to its \"dual morphology,\" this fungus is often misidentified as other fungal species. In this article, we present a case of nephrotic syndrome complicated by an infection with \u003cem\u003eAureobasidium melanogenum\u003c/em\u003e and review previous case reports to enhance the clinical understanding of this pathogen.\u003c/p\u003e","manuscriptTitle":"Aureobasidium melanogenum fungemia in a patient with nephrotic syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-25 06:31:46","doi":"10.21203/rs.3.rs-6847766/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
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