Overventilation-induced airspace acidification increases susceptibility to Pseudomonas pneumonia

Overventilation-induced airspace acidification increases susceptibility to Pseudomonas pneumonia | 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 Overventilation-induced airspace acidification increases susceptibility to Pseudomonas pneumonia Matthias Felten, Chunjiang Tan, Sebastian Ferencik, Jingjing Li, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7105005/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 Ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in critically ill patients. Local pH variations affect bacterial growth. This study investigated the role and mechanisms of airspace acidification by mechanical ventilation (MV) in Pseudomonas aeruginosa (PA)-induced VAP. Mice were subjected to high (HVt:34mL/kg) or low (LVt:9mL/kg) tidal volume MV, intratracheally infected with PA. Alveolar pH was determined via fluorescence microscopy in murine lungs ex vivo. Bacterial growth and adhesion on cyclically stretched A549 and human alveolar epithelial cells was examined. Upon PA infection, HVt mice showed increased alveolo-capillary permeability, elevated lung and blood leukocyte counts, and higher bacterial load in lungs and extrapulmonary organs as compared to LVt controls. HVt MV induced acidification of alveolar lining fluid (ALF) in lungs and decreased pulmonary expression of Na+/H+ exchanger 1 (NHE1). Inhibition of NHE1 enhanced PA growth in vitro on alveolar epithelial cells and increased pulmonary bacterial loads in LVt-MV mice in vivo. In a novel murine VAP model, key characteristics of PA-VAP were replicated. HVt MV induced mild VILI with acidification of airway lining fluid, increasing susceptibility to PA pneumonia. NHE1 was identified as critical factor for MV-induced airspace acidification, and thus as potential target to combat PA-VAP. Health sciences/Diseases/Infectious diseases/Bacterial infection Health sciences/Medical research/Experimental models of disease Health sciences/Medical research/Translational research Health sciences/Health care/Disease prevention/Preventive medicine Ventilator-associated pneumonia Pseudomonas pneumonia mechanical ventilation ARDS airspace acidification Full Text Additional Declarations There is NO Competing Interest. 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. 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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-7105005","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":488463381,"identity":"885dfc2c-75e8-4e37-8322-b8fb21723f3c","order_by":0,"name":"Matthias Felten","email":"data:image/png;base64,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","orcid":"","institution":"Charité - 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Local pH variations affect bacterial growth. This study investigated the role and mechanisms of airspace acidification by mechanical ventilation (MV) in \u003ci\u003ePseudomonas aeruginosa\u003c/i\u003e (PA)-induced VAP. Mice were subjected to high (HVt:34mL/kg) or low (LVt:9mL/kg) tidal volume MV, intratracheally infected with PA. Alveolar pH was determined via fluorescence microscopy in murine lungs ex vivo. Bacterial growth and adhesion on cyclically stretched A549 and human alveolar epithelial cells was examined. Upon PA infection, HVt mice showed increased alveolo-capillary permeability, elevated lung and blood leukocyte counts, and higher bacterial load in lungs and extrapulmonary organs as compared to LVt controls. HVt MV induced acidification of alveolar lining fluid (ALF) in lungs and decreased pulmonary expression of Na+/H+ exchanger 1 (NHE1). Inhibition of NHE1 enhanced PA growth in vitro on alveolar epithelial cells and increased pulmonary bacterial loads in LVt-MV mice in vivo. In a novel murine VAP model, key characteristics of PA-VAP were replicated. HVt MV induced mild VILI with acidification of airway lining fluid, increasing susceptibility to PA pneumonia. NHE1 was identified as critical factor for MV-induced airspace acidification, and thus as potential target to combat PA-VAP.","manuscriptTitle":"Overventilation-induced airspace acidification increases susceptibility to Pseudomonas pneumonia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-22 08:25:53","doi":"10.21203/rs.3.rs-7105005/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":"055bc113-88e2-4845-b40f-47dcec205f2d","owner":[],"postedDate":"July 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51850171,"name":"Health sciences/Diseases/Infectious diseases/Bacterial infection"},{"id":51850172,"name":"Health sciences/Medical research/Experimental models of disease"},{"id":51850173,"name":"Health sciences/Medical research/Translational research"},{"id":51850174,"name":"Health sciences/Health care/Disease prevention/Preventive medicine"}],"tags":[],"updatedAt":"2025-09-16T15:31:04+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-22 08:25:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7105005","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7105005","identity":"rs-7105005","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}