Platelet microbicidal protein enhances antibiotic-induced killing of and postantibiotic effect in Staphylococcus aureus

Abstract

The interaction of bacteria with platelets at the cardiac valve surface represents a critical event in the induction of infective endocarditis. Platelets are thought to modulate induction or propagation of endocarditis via secretion of alpha-granule-derived platelet microbicidal protein (PMP) (a low-molecular-mass, cationic, heat-stable protein distinct from lysozyme). We studied representative PMP-susceptible and PMP-resistant Staphylococcus aureus isolates to determine their in vitro bacteriostatic and bactericidal susceptibilities to combinations of PMP plus antistaphylococcal antibiotics. PMP plus oxacillin exerted a synergistic bactericidal effect, in contrast to either agent alone, regardless of the intrinsic PMP susceptibility of the isolate tested. Exposure of S. aureus to PMP alone resulted in residual postexposure growth-inhibitory effects lasting from 0.9 to 1.8 h. Sequential exposure of S. aureus isolates to PMP for 30 min followed by exposure to either oxacillin or vancomycin (each at 10x the MIC for 120 min) resulted in a significant extension of the postantibiotic-effect duration compared with antibiotic exposure alone (P less than or equal to 0.05). Collectively, these findings indicate that PMP both enhances antibiotic-induced killing of S. aureus and increases the postantibiotic-effect duration in S. aureus.