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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Calb<\/jats:italic>\n                    ) in the lower respiratory tract (LRT) is considered a rare cause of pneumonia, yet its frequent recovery from LRT secretions of mechanically ventilated patients associates with poor clinical outcomes. To determine whether\n                    <jats:italic toggle=\"yes\">Calb<\/jats:italic>\n                    contributes to lung injury, we conducted a translational investigation spanning two independent, prospective human cohorts, murine models of lung injury, and in vitro assays. In critically ill patients,\n                    <jats:italic toggle=\"yes\">Calb<\/jats:italic>\n                    was the most abundant fungus in LRT specimens, and its detection associated with increased markers of lung injury, prolonged mechanical ventilation, and increased mortality. In a murine model, intratracheal\n                    <jats:italic toggle=\"yes\">Calb<\/jats:italic>\n                    was sufficient to disrupt the air-blood barrier and recruit neutrophils, effects markedly attenuated with heat-killed\n                    <jats:italic toggle=\"yes\">Calb<\/jats:italic>\n                    . Neutrophil depletion led to uncontrolled fungal growth, systemic dissemination and mortality, with surviving mice exhibiting worsened barrier disruption, demonstrating that neutrophils support pathogen control while lung injury is driven by the live organism.\n                    <jats:italic toggle=\"yes\">Calb<\/jats:italic>\n                    induced lung epithelial cytotoxicity as well as barrier disruption in human alveolar epithelial cells at air liquid interface. Yeast-locked mutants without hyphal morphogenesis demonstrated attenuated barrier disruption in human alveolar cells and diminished lung injury in mice, despite higher fungal burden. In human cohort data, LRT microbiome profiles with high\n                    <jats:italic toggle=\"yes\">Calb<\/jats:italic>\n                    abundance and codominant bacterial pathogens predicted worse mortality, and mouse models confirmed that\n                    <jats:italic toggle=\"yes\">Calb<\/jats:italic>\n                    amplifies lung barrier disruption when followed by\n                    <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                    inoculation, an effect requiring hyphal morphogenesis. These findings establish that LRT\n                    <jats:italic toggle=\"yes\">Calb<\/jats:italic>\n                    causes direct air-blood barrier disruption through hyphal morphogenesis and amplifies bacterial lung injury, challenging the prevailing view of\n                    <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                    as an innocent respiratory bystander.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2608378123","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:12:05Z","timestamp":1790017925000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["<i>Candida<\/i>\n                    in the lower respiratory tract induces barrier disruption in mice and predicts poor outcomes in mechanically ventilated humans"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2775-780X","authenticated-orcid":false,"given":"Nathanial J.","family":"Tolman","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04ehecz88","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center","place":["Pittsburgh"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0864-6642","authenticated-orcid":false,"given":"Wonseok","family":"Choi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University","place":["Stony 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