Staphylococcus aureus extracellular vesicles carry biologically active β-lactamase

Area of Science:

• Microbiology
• Bacterial Communication
• Antibiotic Resistance

Background:

• Gram-positive bacteria produce extracellular vesicles (EVs).
• The functions of Gram-positive bacterial EVs, particularly in interbacterial interactions and antibiotic resistance, remain largely unexplored.
• Staphylococcus aureus is a key Gram-positive pathogen with significant clinical relevance.

Purpose of the Study:

• To investigate the role of Staphylococcus aureus EVs in mediating interbacterial communication and antibiotic resistance.
• To determine the specific mechanism by which S. aureus EVs confer resistance to ampicillin.
• To assess the protective effect of EVs against other antibiotic classes.

Main Methods:

• S. aureus EVs were isolated and characterized.
• The presence of BlaZ (a beta-lactamase) in EVs was analyzed.
• The ability of S. aureus EVs to confer ampicillin resistance to susceptible bacteria was tested.
• The effect of heat treatment and protease digestion on EV function was evaluated.
• Beta-lactamase activity of soluble and EV-associated BlaZ was compared.

Main Results:

• S. aureus EVs were found to liberate BlaZ, a beta-lactamase protein.
• These EVs conferred ampicillin resistance to susceptible Gram-negative and Gram-positive bacteria.
• EVs did not provide resistance against tetracycline, chloramphenicol, or kanamycin.
• The blaZ gene was not detected within the EVs.
• Heat-treated EVs lost their protective function.
• EV-associated BlaZ showed similar enzymatic activity to soluble BlaZ but was protected from protease digestion.

Conclusions:

• S. aureus EVs play a crucial role in interbacterial communication by delivering functional BlaZ.
• EVs contribute to antibiotic resistance within polymicrobial communities, promoting bacterial survival against ampicillin.
• The protective structure of EVs shields BlaZ activity, enhancing its efficacy in degrading ampicillin.