An In Vitro Cell Culture Model for Pyoverdine-Mediated Virulence

dc.citation.articleNumber9
dc.citation.issueNumber1
dc.citation.journalTitlePathogens
dc.citation.volumeNumber10
dc.contributor.authorKang, Donghoon
dc.contributor.authorKirienko, Natalia V.
dc.date.accessioned2021-02-08T18:37:59Z
dc.date.available2021-02-08T18:37:59Z
dc.date.issued2021
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.
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.
dc.identifier.digitalpathogens-10-00009-v2
dc.identifier.doihttps://doi.org/10.3390/pathogens10010009
dc.identifier.urihttps://hdl.handle.net/1911/109822
dc.language.isoeng
dc.publisherMDPI
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 cited
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.keywordPseudomonas aeruginosa
dc.subject.keywordpyoverdine
dc.subject.keywordmacrophages
dc.subject.keywordvirulence
dc.titleAn In Vitro Cell Culture Model for Pyoverdine-Mediated Virulence
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
pathogens-10-00009-v2.pdf
Size:
2.77 MB
Format:
Adobe Portable Document Format