Subinhibitory Concentrations of Mupirocin Stimulate Staphylococcus aureus Biofilm Formation by Upregulating cidA

Area of Science:

• Microbiology
• Molecular Biology
• Antimicrobial Resistance

Background:

• Subinhibitory antibiotic concentrations can stimulate biofilm formation in multidrug-resistant Staphylococcus aureus (MRSA).
• Mupirocin is a commonly used antibiotic for MRSA infections, but its effect on biofilm formation needs further investigation.

Purpose of the Study:

• To investigate the effect of subinhibitory mupirocin concentrations on biofilm formation in MRSA.
• To elucidate the role of the cidA gene in mupirocin-induced biofilm formation.

Main Methods:

• MRSA strains (USA300 and clinical isolates SA01-SA05) were treated with subinhibitory mupirocin concentrations.
• Biofilm formation was assessed using crystal violet staining and confocal laser scanning microscopy (CLSM).
• Gene expression of cidA was quantified using quantitative real-time PCR (RT-qPCR), and a cidA-deficient mutant was generated and tested.

Main Results:

• Mupirocin treatment increased MRSA attachment and biofilm thickness, correlating with extracellular DNA (eDNA) production.
• RT-qPCR showed a significant upregulation of cidA gene expression (6.05- to 35.52-fold increase) after mupirocin exposure.
• A cidA-deficient mutant did not exhibit increased biofilm formation upon mupirocin exposure, unlike the parent strain.

Conclusions:

• Mupirocin at subinhibitory concentrations stimulates biofilm formation in MRSA.
• The upregulation of the cidA gene, encoding holin-like and antiholin-like proteins, is a key mechanism in mupirocin-induced MRSA biofilm formation.
• Targeting cidA may offer a strategy to prevent or treat MRSA biofilm-related infections.