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Sub-inhibitory concentrations of oxacillin modulate biogenesis and function of extracellular vesicles secreted by

Zhaoxia Ran1,2, Minghui Hao1, Binxin Guo1

  • 1Department of Laboratory Medicine, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.

Frontiers in Microbiology
|August 20, 2025
PubMed
Abstract

Insights

Sub-inhibitory oxacillin boosts Staphylococcus aureus extracellular vesicle (EV) release and alters their protein content. These modified EVs enhance bacterial virulence, impacting host-pathogen interactions.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Extracellular Vesicles

Background:

  • Staphylococcus aureus (S. aureus) extracellular vesicles (EVs) contain toxins and resistance determinants.
  • Production of EV components is influenced by beta-lactam antibiotics.
  • Limited studies exist on beta-lactam effects on EV release and function.

Purpose of the Study:

  • To investigate the impact of sub-inhibitory oxacillin concentrations on S. aureus EV secretion and function.
  • To analyze proteomic changes in oxacillin-induced EVs (OI-EVs).
  • To assess functional alterations in OI-EVs related to pathogenicity.

Main Methods:

  • Isolation of EVs from OS-MRSA (OS-200) strain via ultracentrifugation.
  • Proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  • Functional assays including erythrocyte hemolysis, biofilm formation, cytokine measurement, and cell invasion.

Main Results:

  • Sub-inhibitory oxacillin significantly increased OI-EV secretion and protein abundance (e.g., PBP2, EmrB, Hlg, enolase) in a dose-dependent manner.
  • OI-EVs exhibited enhanced hemolytic activity, promoted biofilm formation, and stimulated pro-inflammatory cytokine secretion (IL-6, TNF-α).
  • OI-EVs demonstrated increased invasion potential into lung epithelial cells.

Conclusions:

  • Sub-inhibitory oxacillin alters S. aureus EV secretion and composition.
  • A novel link exists between antimicrobial exposure, EV biogenesis, and S. aureus pathogenicity.
  • Findings offer insights into how beta-lactams modulate bacterial vesicles, influencing host-pathogen interactions.
Keywords:
OS-MRSAbioactivitiesextracellular vesiclesoxacillinsub-inhibitory concentrations

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