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Platelet microbicidal protein enhances antibiotic-induced killing of and postantibiotic effect in Staphylococcus
M R Yeaman1, D C Norman, A S Bayer
1Department of Medicine, Harbor-UCLA Medical Center, Torrance 90509.
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.
Insights
Platelet microbicidal protein (PMP) enhances antibiotic killing of Staphylococcus aureus and prolongs antibiotic effectiveness. This synergy is crucial for treating infective endocarditis.
Area of Science:
- Microbiology
- Infectious Diseases
- Cardiovascular Medicine
Background:
- Bacterial interaction with cardiac valve platelets initiates infective endocarditis.
- Platelet microbicidal protein (PMP) may modulate endocarditis via its antimicrobial properties.
Purpose of the Study:
- To investigate the in vitro synergistic effects of PMP and antibiotics against Staphylococcus aureus.
- To determine PMP's impact on antibiotic efficacy and postantibiotic effect duration.
Main Methods:
- Testing PMP susceptibility and resistance in Staphylococcus aureus isolates.
- Evaluating in vitro bacteriostatic and bactericidal effects of PMP combined with oxacillin or vancomycin.
- Assessing the duration of the postantibiotic effect after sequential PMP and antibiotic exposure.
Main Results:
- PMP and oxacillin demonstrated synergistic bactericidal effects against Staphylococcus aureus, irrespective of PMP susceptibility.
- Exposure to PMP alone induced a residual growth inhibition in Staphylococcus aureus for 0.9–1.8 hours.
- Sequential exposure to PMP followed by oxacillin or vancomycin significantly extended the postantibiotic effect duration.
Conclusions:
- PMP enhances antibiotic-induced killing of Staphylococcus aureus.
- PMP increases the duration of the postantibiotic effect for Staphylococcus aureus, suggesting a potential therapeutic role in endocarditis treatment.