Antibiotics Stimulate Formation of Vesicles inStaphylococcus aureusin both Phage-Dependent and -Independent Fashions and via Different Routes
ABSTRACTBacterial membrane vesicle research has so far focused mainly on Gram-negative bacteria. Only recently have Gram-positive bacteria been demonstrated to produce and release extracellular membrane vesicles (MVs) that contribute to bacterial virulence. Although treatment of bacteria with antibiotics is a well-established trigger of bacterial MV formation, the underlying mechanisms are poorly understood. In this study, we show that antibiotics can induce MVs through different routes in the important human pathogenStaphylococcus aureus. DNA-damaging agents and antibiotics inducing the SOS response triggered vesicle formation in lysogenic strains ofS. aureusbut not in their phage-devoid counterparts. The β-lactam antibiotics flucloxacillin and ceftaroline increased vesicle formation in a prophage-independent manner by weakening the peptidoglycan layer. We present evidence that the amount of DNA associated with MVs formed by phage lysis is greater than that for MVs formed by β-lactam antibiotic-induced blebbing. The purified MVs derived fromS. aureusprotected the bacteria from challenge with daptomycin, a membrane-targeting antibiotic, bothin vitroandex vivoin whole blood. In addition, the MVs protectedS. aureusfrom killing in whole blood, indicating that antibiotic-induced MVs function as a decoy and thereby contribute to the survival of the bacterium.