Cross-Species Protection to Innate Immunity Mediated by A Bacterial Pigment

Area of Science:

• Microbiology
• Infectious Diseases
• Bacterial Interactions

Background:

• Polymicrobial bacterial infections, particularly chronic co-infections involving *Staphylococcus aureus* and *Pseudomonas aeruginosa*, present significant clinical challenges.
• Understanding the molecular mechanisms governing these complex interactions is crucial for developing effective therapeutic strategies.

Approach:

• Investigated the role of *P. aeruginosa* exoproduct 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) in modulating *S. aureus* staphyloxanthin (STX) production.
• Assessed the impact of STX on pathogen survival against oxidative stress and phagocytosis by human neutrophils.
• Evaluated the role of STX in a murine wound co-infection model.

Key Points:

• *P. aeruginosa* HQNO directly induces STX production in *S. aureus*, a conserved phenotype in clinical isolates.
• STX production by *S. aureus* significantly enhances *P. aeruginosa* survival against hydrogen peroxide and human neutrophils.
• Co-infection with wild-type *S. aureus*, but not a STX-deficient mutant, increased *P. aeruginosa* burden and disease severity in a murine wound model.

Conclusions:

• Discovered a novel mechanism where *P. aeruginosa* HQNO mediates polymicrobial interactions by inducing *S. aureus* STX production.
• STX induction confers a survival advantage to both pathogens against innate immune effectors, promoting co-infection progression.
• This study advances the understanding of cooperative bacterial pathogenesis in polymicrobial infections.