In vitro lung epithelial cell model reveals novel roles for Pseudomonas aeruginosa siderophores

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dc.citation.articleNumbere03693-23en_US
dc.citation.issueNumber3en_US
dc.citation.journalTitleMicrobiology Spectrumen_US
dc.citation.volumeNumber12en_US
dc.contributor.authorKang, Donghoonen_US
dc.contributor.authorXu, Qien_US
dc.contributor.authorKirienko, Natalia V.en_US
dc.date.accessioned2024-07-25T20:56:28Zen_US
dc.date.available2024-07-25T20:56:28Zen_US
dc.date.issued2024en_US
dc.description.abstractThe multidrug-resistant pathogen Pseudomonas aeruginosa is a common nosocomial respiratory pathogen that continues to threaten the lives of patients with mechanical ventilation in intensive care units and those with underlying comorbidities such as cystic fibrosis or chronic obstructive pulmonary disease. For over 20 years, studies have repeatedly demonstrated that the major siderophore pyoverdine is an important virulence factor for P. aeruginosa in invertebrate and mammalian hosts in vivo. Despite its physiological significance, an in vitro, mammalian cell culture model that can be used to characterize the impact and molecular mechanisms of pyoverdine-mediated virulence has only been developed very recently. In this study, we adapt a previously-established, murine macrophage-based model to use human bronchial epithelial (16HBE) cellsWe demonstrate that conditioned medium from P. aeruginosa induced rapid 16HBE cell death through the pyoverdine-dependent secretion of cytotoxic rhamnolipids. Genetic or chemical disruption of pyoverdine biosynthesis decreased rhamnolipid production and mitigated cell death. Consistent with these observations, chemical depletion of lipids or genetic disruption of rhamnolipid biosynthesis abrogated the toxicity of the conditioned medium. Furthermore, we also examine the effects of exposure to purified pyoverdine on 16HBE cells. While pyoverdine accumulated within cells, it was largely sequestered within early endosomes, resulting in minimal cytotoxicity. More membrane-permeable iron chelators, such as the siderophore pyochelin, decreased epithelial cell viability and upregulated several pro-inflammatory genes. However, pyoverdine potentiated these iron chelators in activating pro-inflammatory pathways. Altogether, these findings suggest that the siderophores pyoverdine and pyochelin play distinct roles in virulence during acute P. aeruginosa lung infection.en_US
dc.identifier.citationKang, D., Xu, Q., & Kirienko, N. V. (2024). In vitro lung epithelial cell model reveals novel roles for Pseudomonas aeruginosa siderophores. Microbiology Spectrum, 12(3), e03693-23. https://doi.org/10.1128/spectrum.03693-23en_US
dc.identifier.digitalkang-et-al-2024-in-vitro-lung-epithelial-cellen_US
dc.identifier.doihttps://doi.org/10.1128/spectrum.03693-23en_US
dc.identifier.urihttps://hdl.handle.net/1911/117540en_US
dc.language.isoengen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleIn vitro lung epithelial cell model reveals novel roles for Pseudomonas aeruginosa siderophoresen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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