933 Staphylococcus aureus reversibly regulates Agr quorum sensing to cause an outbreak in a hospital

Staphylococcus aureus causes hospital outbreaks and becomes multi-drug resistant, although how bacteria adapt to environments remains unknown. We collected S. isolates during an outbreak in a hospital. performed the whole-genome sequence found most are same clone’s descendants. Though original clone showed functional accessory gene regulator (Agr) that enables various toxin productions upon sensing high population density, offspring subclones silenced Agr completely or reversibly; latter group, newly termed environmentally-adapted (EA)-Agr aureus, was mainly isolated late phase of acquired additional antibiotic resistance. EA-Agr were genetically identical Agr-expressing but different ribosomal DNA methylation. Agr-silencing (EA-Agr agr mutant) incidence persisters, which is dormant surviving under antibiotics, compared (P<0.01). When transformed with plasmids, incorporated exogenous more efficiently than On other hand, survived better mutant inside macrophages vitro Moreover, systemic infection mouse model, did not kill mice (P<0.01, survival rate) elicited weak host inflammatory response (P<0.05). Importantly, only persistently colonized abdominal cavity (P<0.001) positive subclones. Collectively, increased ability tolerate acquire antibiotic-resistance, escape immunity colonize mice. Thus, flexible regulation promotes resistance adaptation environment.