An In Vitro Cell Culture Model for Pyoverdine-Mediated Virulence

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dc.citation.articleNumber9en_US
dc.citation.issueNumber1en_US
dc.citation.journalTitlePathogensen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorKang, Donghoonen_US
dc.contributor.authorKirienko, Natalia V.en_US
dc.date.accessioned2021-02-08T18:37:59Zen_US
dc.date.available2021-02-08T18:37:59Zen_US
dc.date.issued2021en_US
dc.description.abstractPseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen that utilizes a wide-range of virulence factors to cause acute, life-threatening infections in immunocompromised patients, especially those in intensive care units. It also causes debilitating chronic infections that shorten lives and worsen the quality of life for cystic fibrosis patients. One of the key virulence factors in P. aeruginosa is the siderophore pyoverdine, which provides the pathogen with iron during infection, regulates the production of secreted toxins, and disrupts host iron and mitochondrial homeostasis. These roles have been characterized in model organisms such as Caenorhabditis elegans and mice. However, an intermediary system, using cell culture to investigate the activity of this siderophore has been absent. In this report, we describe such a system, using murine macrophages treated with pyoverdine. We demonstrate that pyoverdine-rich filtrates from P. aeruginosa exhibit substantial cytotoxicity, and that the inhibition of pyoverdine production (genetic or chemical) is sufficient to mitigate virulence. Furthermore, consistent with previous observations made in C. elegans, pyoverdine translocates into cells and disrupts host mitochondrial homeostasis. Most importantly, we observe a strong correlation between pyoverdine production and virulence in P. aeruginosa clinical isolates, confirming pyoverdine’s value as a promising target for therapeutic intervention. This in vitro cell culture model will allow rapid validation of pyoverdine antivirulents in a simple but physiologically relevant manner.en_US
dc.identifier.citationKang, Donghoon and Kirienko, Natalia V.. "An In Vitro Cell Culture Model for Pyoverdine-Mediated Virulence." <i>Pathogens,</i> 10, no. 1 (2021) MDPI: https://doi.org/10.3390/pathogens10010009.en_US
dc.identifier.digitalpathogens-10-00009-v2en_US
dc.identifier.doihttps://doi.org/10.3390/pathogens10010009en_US
dc.identifier.urihttps://hdl.handle.net/1911/109822en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsThis is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citeden_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subject.keywordPseudomonas aeruginosaen_US
dc.subject.keywordpyoverdineen_US
dc.subject.keywordmacrophagesen_US
dc.subject.keywordvirulenceen_US
dc.titleAn In Vitro Cell Culture Model for Pyoverdine-Mediated Virulenceen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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