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

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dc.citation.articleNumbere03693-23
dc.citation.issueNumber3
dc.citation.journalTitleMicrobiology Spectrum
dc.citation.volumeNumber12
dc.contributor.authorKang, Donghoon
dc.contributor.authorXu, Qi
dc.contributor.authorKirienko, Natalia V.
dc.date.accessioned2024-07-25T20:56:28Z
dc.date.available2024-07-25T20:56:28Z
dc.date.issued2024
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.
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.03693-23
dc.identifier.digitalkang-et-al-2024-in-vitro-lung-epithelial-cell
dc.identifier.doihttps://doi.org/10.1128/spectrum.03693-23
dc.identifier.urihttps://hdl.handle.net/1911/117540
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleIn vitro lung epithelial cell model reveals novel roles for Pseudomonas aeruginosa siderophores
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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