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

Authors
  • Wong, Tak-Wah1, 2
  • Liao, Shu-Zhen1
  • Ko, Wen-Chien3
  • Wu, Chi-Jung3, 4
  • Wu, Shin Bei1
  • Chuang, Yin-Ching5
  • Huang, I-Hsiu6
  • 1 (S.B.W.)
  • 2 Center of Applied Nanomedicine, National Cheng Kung University, Tainan 70101, Taiwan
  • 3 (C.-J.W.)
  • 4 National Institutes of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 70456, Taiwan
  • 5 Department of Medical Research, Chi Mei Medical Center, Tainan 72263, Taiwan
  • 6 Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Type
Published Article
Journal
Journal of Clinical Medicine
Publisher
MDPI AG
Publication Date
Mar 25, 2019
Volume
8
Issue
3
Identifiers
DOI: 10.3390/jcm8030411
PMID: 30934605
PMCID: PMC6463108
Source
PubMed Central
Keywords
License
Green

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.

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