Corynebacterium pseudodiphtheriticum Exploits Staphylococcus aureus Virulence Components in a Novel Polymicrobial Defense Strategy

Commensal bacteria in the human nasal cavity are known to suppress opportunistic pathogen colonization by competing for limited space and nutrients. It has become increasingly apparent that some commensal bacteria also produce toxic compounds that directly inhibit or kill incoming competitors. Numerous studies suggest that microbial species-specific interactions can affect human nasal colonization by the opportunistic pathogen However, the complex and dynamic molecular interactions that mediate these effects on nasal colonization are often difficult to study and remain poorly understood. Here, we show that , a common member of the normal nasal microbiota, mediates contact-independent bactericidal activity against , including methicillin-resistant (MRSA). Bacterial interaction assays revealed that isolates that were spontaneously resistant to killing could be recovered at a low frequency. To better understand the pathways associated with killing and resistance, a transposon mutant library was utilized to select for resistant mutant strains. We found that insertional inactivation of , which codes for the sensor kinase of the Agr quorum sensing (Agr QS) system that regulates expression of many virulence factors in , conferred resistance to killing. Analysis of the spontaneously resistant isolates revealed that each showed decreased expression of the Agr QS components. Targeted analysis of pathways regulated by Agr QS revealed that loss of the phenol-soluble modulins (PSMs), which are effectors of Agr QS, also conferred resistance to bactericidal activity. Transmission electron microscopy analysis revealed that induced dramatic changes to cell surface morphology that likely resulted in cell lysis. Taken together, these data suggest that -mediated killing of requires virulence components. While can overcome targeted killing, this occurs at the cost of attenuated virulence; loss of Agr QS activity would phenotypically resemble a commensal state that would be unlikely to be associated with disease. Commensal competition resulting in dampened virulence of the competitor may represent an exciting and unexplored possibility for development of novel antimicrobial compounds. While some individuals are nasally colonized with , the underlying factors that determine colonization are not understood. There is increasing evidence that indicates that resident bacteria play a role; some commensal species can eradicate from the nasal cavity. Among these, can eliminate from the