A bacterial pigment provides cross-species protection from H2O2- and neutrophil-mediated killing

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dc.contributor.authorLiu, Yiweien
dc.contributor.authorMcQuillen, Eleanor A.en
dc.contributor.authorRana, Pranav S. J. B.en
dc.contributor.authorGloag, Erin S.en
dc.contributor.authorParsek, Matthew R.en
dc.contributor.authorWozniak, Daniel J.en
dc.date.accessioned2024-01-22T20:32:10Zen
dc.date.available2024-01-22T20:32:10Zen
dc.date.issued2024-01-03en
dc.description.abstractBacterial infections are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus cause chronic co-infections, which are more problematic than mono-species infections. Understanding the mechanisms of their interactions is crucial for treating co-infections. Staphyloxanthin (STX), a yellow pigment synthesized by the S. aureus crt operon, promotes S. aureus resistance to oxidative stress and neutrophil-mediated killing. We found that STX production by S. aureus, either as surface-grown macrocolonies or planktonic cultures, was elevated when exposed to the P. aeruginosa exoproduct, 2-heptyl- 4- hydroxyquinoline N-oxide (HQNO). This was observed with both mucoid and non-mucoid P. aeruginosa strains. The induction phenotype was found in a majority of P. aeruginosa and S. aureus clinical isolates examined. When subjected to hydrogen peroxide or human neutrophils, P. aeruginosa survival was significantly higher when mixed with wild-type (WT) S. aureus, compared to P. aeruginosa alone or with an S. aureus crt mutant deficient in STX production. In a murine wound model, co-infection with WT S. aureus, but not the STX-deficient mutant, enhanced P. aeruginosa burden and disease compared to mono-infection. In conclusion, we identified a role for P. aeruginosa HQNO mediating polymicrobial interactions with S. aureus by inducing STX production, which consequently promotes resistance to the innate immune effectors H2O2 and neutrophils. These results further our understanding of how different bacterial species cooperatively cause co-infections.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1073/pnas.2312334121en
dc.identifier.eissn1091-6490en
dc.identifier.issn0027-8424en
dc.identifier.issue2en
dc.identifier.orcidGloag, Erin [0000-0001-8895-3444]en
dc.identifier.urihttps://hdl.handle.net/10919/117585en
dc.identifier.volume121en
dc.language.isoenen
dc.publisherProceedings of the National Academy of Sciencesen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleA bacterial pigment provides cross-species protection from H<sub>2</sub>O<sub>2</sub>- and neutrophil-mediated killingen
dc.title.serialProceedings of the National Academy of Sciencesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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