Pyoverdine Inhibitors and Gallium Nitrate Synergistically Affect Pseudomonas aeruginosa

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dc.citation.issueNumber3
dc.citation.journalTitlemSphere
dc.citation.volumeNumber6
dc.contributor.authorKang, Donghoon
dc.contributor.authorRevtovich, Alexey V.
dc.contributor.authorDeyanov, Alexander E.
dc.contributor.authorKirienko, Natalia V.
dc.date.accessioned2022-01-21T16:24:04Z
dc.date.available2022-01-21T16:24:04Z
dc.date.issued2021
dc.description.abstractPseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen that frequently causes ventilator-associated pneumonia in intensive care units and chronic lung infections in cystic fibrosis patients. The rising prevalence of drug-resistant bacteria demands the exploration of new therapeutic avenues for treating P. aeruginosa infections. Perhaps the most thoroughly explored alternative is to use novel treatments to target pathogen virulence factors, like biofilm or toxin production. Gallium(III) nitrate is one such agent. It has been recognized for its ability to inhibit pathogen growth and biofilm formation in P. aeruginosa by disrupting bacterial iron homeostasis. However, irreversible sequestration by pyoverdine substantially limits its effectiveness. In this report, we show that disrupting pyoverdine production (genetically or chemically) potentiates the efficacy of gallium nitrate. Interestingly, we report that the pyoverdine inhibitor 5-fluorocytosine primarily functions as an antivirulent, even when it indirectly affects bacterial growth in the presence of gallium, and that low selective pressure for resistance occurs. We also demonstrate that the antibiotic tetracycline inhibits pyoverdine at concentrations below those required to prevent bacterial growth, and this activity allows it to synergize with gallium to inhibit bacterial growth and rescue Caenorhabditis elegans during P. aeruginosa pathogenesis.
dc.identifier.citationKang, Donghoon, Revtovich, Alexey V., Deyanov, Alexander E., et al.. "Pyoverdine Inhibitors and Gallium Nitrate Synergistically Affect Pseudomonas aeruginosa." <i>mSphere,</i> 6, no. 3 (2021) American Society for Microbiology: https://doi.org/10.1128/mSphere.00401-21.
dc.identifier.digitalmSphere-00401-21
dc.identifier.doihttps://doi.org/10.1128/mSphere.00401-21
dc.identifier.urihttps://hdl.handle.net/1911/111937
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.rightsThis is an open- access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titlePyoverdine Inhibitors and Gallium Nitrate Synergistically Affect Pseudomonas aeruginosa
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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