Indocyanine Green-Mediated Photodynamic Therapy Reduces Methicillin-Resistant Staphylococcus aureus Drug Resistance

Area of Science:

• Microbiology
• Photomedicine
• Infectious Diseases

Background:

• Methicillin-resistant Staphylococcus aureus (MRSA) causes severe skin and wound infections.
• Photodynamic therapy (PDT) with indocyanine green (ICG) shows promise for killing MRSA.
• The impact of ICG-PDT on MRSA drug sensitivity is not well understood.

Purpose of the Study:

• To investigate the effects of ICG-PDT on the drug sensitivity of MRSA.
• To analyze changes in MRSA growth rate, cell wall thickness, and gene expression post-ICG-PDT.
• To evaluate the therapeutic potential of ICG-PDT combined with oxacillin in an animal model.

Main Methods:

• Analysis of drug-sensitivity phenotypes, growth rates, and cell-wall thickness of MRSA strains after ICG-PDT.
• Gene expression analysis using PCR and qRT-PCR.
• Protein expression analysis via immunoblotting.
• In vivo evaluation of drug sensitivity and wound healing in animal models.

Main Results:

• MRSA surviving ICG-PDT exhibited increased growth rates and thinner cell walls.
• These surviving MRSA strains demonstrated enhanced sensitivity to oxacillin, linked to mecA complex gene deletion.
• ICG-PDT treatment led to reduced skin necrosis and faster healing in infected animal models.
• Combination therapy with oxacillin eradicated MRSA from lung tissue in a mouse model.

Conclusions:

• ICG-PDT treatment induces a shift towards an oxacillin-sensitive phenotype in MRSA.
• ICG-PDT holds potential as a standalone or adjuvant therapy for MRSA wound infections.
• This approach may help overcome antibiotic resistance in MRSA infections.