Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) skin-wound infections are associated with considerable morbidity and mortality. Indocyanine green (ICG), a safe and inexpensive dye used in clinical imaging, can be activated by near-infrared in photodynamic therapy (PDT) and photothermal therapy (PTT) to effectively kill MRSA. However, how this treatment affects MRSA drug sensitivity remains unknown. The drug-sensitivity phenotypes, bacterial growth rate, and cell-wall thickness of three MRSA strains were analyzed after ICG-PDT. Drug-resistant gene expressions were determined by polymerase chain reaction (PCR) and quantitative reverse transcription (qRT)-PCR. Related protein expressions were examined with immunoblotting. Drug sensitivity was further evaluated in animal models. MRSA that survived the treatment grew faster, and the cell wall became thinner compared to parental cells. These cells became more sensitive to oxacillin, which was partly related to mecA complex gene deletion. Skin necrosis caused by ICG-PDT-treated MRSA infection was smaller and healed faster than that infected with parental cells. With oxacillin therapy, no bacteria could be isolated from mouse lung tissue infected with ICG-PDT-treated MRSA. ICG-PDT drives MRSA toward an oxacillin-sensitive phenotype. It has the potential to develop into an alternative or adjuvant clinical treatment against MRSA wound infections.
Highlights
Staphylococcus aureus is a gram-positive normal resident flora of the human skin and respiratory tract that causes a wide range of clinical infections [1,2]
We have shown that methicillin-resistant S. aureus (MRSA) pretreated with 0.1% H2O2 before Indocyanine green (ICG)-photodynamic therapy (PDT) reduced MRSA growth by seven logs with a light intensity that was harmless to human fibroblasts [26]
To mimic the clinical scenario in which many MRSA may survive after a low dose of ICG-PDT, three MRSA isolates were subjected to less bactericidal ICG-PDT treatment
Summary
Staphylococcus aureus is a gram-positive normal resident flora of the human skin and respiratory tract that causes a wide range of clinical infections [1,2]. In the United States, the annual incidence of S. aureus bacteremia is 4–38 per 100,000 person years. The 30-day all-cause mortality of S. aureus bacteremia is 20% [3,4]. In the 1940s, S. aureus was sensitive to penicillin, a β-lactam antibiotic that inhibits the formation of peptidoglycan crosslinks in the bacterial cell wall and leads to cell death [5]. The first methicillin-resistant S. aureus (MRSA) was isolated in the UK in 1961 [6]. MRSA infections have become one of the most concerning global health issues because of the high mortality, long hospital stays, and high healthcare costs
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