Nonconformity of biofilm formation in vivo and in vitro based on Staphylococcus aureus accessory gene regulator status

Staphylococcus aureus is an opportunistic, pathogenic bacteria that causes significant morbidity and mortality. As antibiotic resistance by S. aureus continues to be a serious concern, developing novel drug therapies to combat these infections is vital. Quorum sensing inhibitors (QSI) dampen S. aureus virulence and facilitate clearance by the host immune system by blocking quorum sensing signaling that promotes upregulation of virulence genes controlled by the accessory gene regulator (agr) operon. While QSIs have shown therapeutic promise in mouse models of S. aureus skin infection, their further development has been hampered by the suggestion that agr inhibition promotes biofilm formation. In these studies, we investigated the relationship between agr function and biofilm growth across various S. aureus strains and experimental conditions, including in a mouse model of implant-associated infection. We found that agr deletion was associated with the presence of increased biofilm only under narrow in vitro conditions and, crucially, was not associated with enhanced biofilm development or enhanced morbidity in vivo.