Fig. 5: Model of the role of QS (Agr) mutant development during staphylococcal device-associated infection.

Naturally, skin-colonizing S. aureus contaminates the indwelling medical device (shown as a subcutaneous catheter, as an example) during insertion. Initial colonization of the device by contaminating bacteria ensues. Spontaneous mutations in the agr locus happen in some bacteria, producing Agr-dysfunctional S. aureus. During prolonged infection under selective pressure by antibiotics (vancomycin, levofloxacin), Agr-dysfunctional mutants outgrow wild-type members of the population. As a result, a strong biofilm forms, considerably increasing antibiotic resistance and resistance to leukocyte attacks. This leads to the exacerbation of device infection, which can involve bacteremia and systemic dissemination.