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

Bacterial 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 yell...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2024-01, Vol.121 (2), p.1-e2312334121
Main Authors: Liu, Yiwei, McQuillen, Eleanor A, Rana, Pranav S J B, Gloag, Erin S, Parsek, Matthew R, Wozniak, Daniel J
Format: Article
Language:English
Subjects:
Bacteria
Bacterial diseases
Bacterial infections
Clinical isolates
Deficient mutant
Hydrogen peroxide
Hydroxyquinoline
Leukocytes (neutrophilic)
Neutrophils
Oxidation resistance
Oxidative stress
Phenotypes
Pigments
Protected species
Pseudomonas aeruginosa
Staphylococcus aureus
Staphylococcus infections
Wound infection
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Summary:Bacterial 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2312334121