Competition between Pseudomonas aeruginosa and Staphylococcus aureus is dependent on intercellular signaling and...

Area of Science:

• Microbiology
• Infectious Diseases
• Bacterial Pathogenesis

Background:

• Pseudomonas aeruginosa and Staphylococcus aureus are common co-infecting pathogens in conditions like cystic fibrosis and chronic wounds.
• Previous research indicated P. aeruginosa possesses an in vitro competitive advantage over S. aureus, though this is diminished in vivo.

Purpose of the Study:

• To investigate the role of the two-component regulatory system NtrBC in mediating the competitive advantage of P. aeruginosa over S. aureus during co-infection.
• To elucidate the mechanisms by which NtrBC influences interspecies interactions and virulence factor production.

Main Methods:

• Utilized skin organoid and mouse models for P. aeruginosa and S. aureus co-infection studies.
• Analyzed gene expression of ntrBC during co-culture and in response to N-acetylglucosamine.
• Compared wild-type and mutant P. aeruginosa strains (ΔntrC, ΔntrBC) for their ability to lyse and outcompete S. aureus in planktonic and biofilm settings.
• Assessed the impact of NtrBC on the production of virulence factors and the effect of quorum sensing molecules.

Main Results:

• The NtrBC system was found to be critical for P. aeruginosa's competitive advantage over S. aureus in both in vitro and in vivo models.
• NtrBC expression was induced by co-culture and by N-acetylglucosamine released from lysed S. aureus.
• P. aeruginosa wild-type strains, but not NtrBC mutants, induced S. aureus lysis and outcompeted it in biofilms.
• NtrBC mutants exhibited reduced production of anti-staphylococcal factors like pyoverdine, pyocyanin, and elastase, which could be partially restored by quorum sensing molecule overexpression.

Conclusions:

• The NtrBC two-component system is a key regulator enabling Pseudomonas aeruginosa to gain a competitive edge over Staphylococcus aureus.
• Interspecies signaling, particularly through metabolites like N-acetylglucosamine, activates NtrBC, influencing virulence factor secretion and bacterial competition.
• Understanding the NtrBC system offers potential targets for therapeutic strategies aimed at disrupting P. aeruginosa's dominance in polymicrobial infections.