Staphylococcus aureus Extracellular Vesicles Carry Biologically Active β-Lactamase

Abstract

ABSTRACTGram-positive bacteria naturally produce extracellular vesicles. However, little is known regarding the functions of Gram-positive bacterial extracellular vesicles, especially in the bacterial community. Here, we investigated the role ofStaphylococcus aureusextracellular vesicles in interbacterial communication to cope with antibiotic stress. We found thatS. aureusliberated BlaZ, a β-lactamase protein, via extracellular vesicles. These extracellular vesicles enabled other ampicillin-susceptible Gram-negative and Gram-positive bacteria to survive in the presence of ampicillin. However,S. aureusextracellular vesicles did not mediate the survival of tetracycline-, chloramphenicol-, or kanamycin-susceptible bacteria. Moreover,S. aureusextracellular vesicles did not contain theblaZgene. In addition, the heat-treatedS. aureusextracellular vesicles did not mediate the survival of ampicillin-susceptible bacteria. The β-lactamase activities ofS. aureussoluble and extracellular vesicle-associated BlaZ were similar, but only the extracellular vesicle-associated BlaZ was resistant to protease digestion, which suggests that the enzymatic activity of BlaZ in extracellular vesicles is largely protected by the vesicle structure. Our observations provide evidence of the important role ofS. aureusextracellular vesicles in antibiotic resistance, which allows the polymicrobial community to continue to evolve and prosper against antibiotics.