XerC Contributes to Diverse Forms of Staphylococcus aureus Infection viaagr-Dependent andagr-Independent Pathways
We demonstrate that mutation ofxerC, which reportedly encodes a homologue of anEscherichia colirecombinase, limits biofilm formation in the methicillin-resistantStaphylococcus aureusstrain LAC and the methicillin-sensitive strain UAMS-1. This was not due to the decreased production of the polysaccharide intracellular adhesin (PIA) in either strain because the amount of PIA was increased in a UAMS-1xerCmutant and undetectable in both LAC and its isogenicxerCmutant. Mutation ofxerCalso resulted in the increased production of extracellular proteases and nucleases in both LAC and UAMS-1, and limiting the production of either class of enzymes increased biofilm formation in the isogenicxerCmutants. More importantly, the limited capacity to form a biofilm was correlated with increased antibiotic susceptibility in both strains in the context of an established biofilmin vivo. Mutation ofxerCalso attenuated virulence in a murine bacteremia model, as assessed on the basis of the bacterial loads in internal organs and overall lethality. It also resulted in the decreased accumulation of alpha toxin and the increased accumulation of protein A. These findings suggest thatxerCmay impact the functional status ofagr. This was confirmed by demonstrating the reduced accumulation of RNAIII and AgrA in LAC and UAMS-1xerCmutants. However, this cannot account for the biofilm-deficient phenotype ofxerCmutants because mutation ofagrdid not limit biofilm formation in either strain. These results demonstrate thatxerCcontributes to biofilm-associated infections and acute bacteremia and that this is likely due toagr-independent and -dependent pathways, respectively.