title: Staphylococcus aureus extracellular vesicles carry biologically active β-lactamase.
abstract: Gram-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 of Staphylococcus aureus extracellular vesicles in interbacterial communication to cope with antibiotic stress. We found that S. aureus liberated 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. aureus extracellular vesicles did not mediate the survival of tetracycline-, chloramphenicol-, or kanamycin-susceptible bacteria. Moreover, S. aureus extracellular vesicles did not contain the blaZ gene. In addition, the heat-treated S. aureus extracellular vesicles did not mediate the survival of ampicillin-susceptible bacteria. The β-lactamase activities of S. aureus soluble 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 of S. aureus extracellular vesicles in antibiotic resistance, which allows the polymicrobial community to continue to evolve and prosper against antibiotics.
authors.affiliation: Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Jaewook
authors.initials: J
authors.lastname: Lee
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Lee
authors.forename: Si-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Dae-Kyum
authors.initials: DK
authors.lastname: Kim
authors.forename: Kyong-Su
authors.initials: KS
authors.lastname: Park
authors.forename: Kwang Pyo
authors.initials: KP
authors.lastname: Kim
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Roh
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D005110:Extracellular Space / Q000201:enzymology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011510:Proteolipids / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D001618:beta-Lactamases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D011510:Proteolipids; D000667:Ampicillin; D001618:beta-Lactamases