ALA_PDT Promotes Ferroptosis-Like Death of Mycobacterium abscessus and Antibiotic Sterilization via Oxidative Stress

is one of the common clinical non-tuberculous mycobacteria (NTM) that can cause severe skin infection. 5-Aminolevulinic acid photodynamic therapy (ALA_PDT) is an emerging effective antimicrobial treatment. To explore whether ALA_PDT can be used to treat infections, we conducted a series of experimen...

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Bibliographic Details
Published in:Antioxidants 2022-03, Vol.11 (3), p.546
Main Authors: Wang, Xiaoyu, Wan, Meiyin, Zhang, Lei, Dai, Yongdong, Hai, Yang, Yue, Chenda, Xu, Junqi, Ding, Yadan, Wang, Mei, Xie, Jianping, Lei, Xia, Zhong, Julia-Li
Format: Article
Language:English
Subjects:
Abscesses
Acetylcysteine
ALA_PDT
Aminolevulinic acid
antibiotic resistance
Antibiotics
Bacteria
Cell membranes
Death
DNA damage
Drug resistance
Ferroptosis
Glycerol
Heme
heme oxygenase MAB_4773
Infections
Iron
Light therapy
Lipid peroxidation
Lipids
Membrane permeability
Mycobacterium abscessus
Oxidative stress
Oxygenase
Photodynamic therapy
Plasmids
Sterilization
Transcription
Tuberculosis
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Summary:is one of the common clinical non-tuberculous mycobacteria (NTM) that can cause severe skin infection. 5-Aminolevulinic acid photodynamic therapy (ALA_PDT) is an emerging effective antimicrobial treatment. To explore whether ALA_PDT can be used to treat infections, we conducted a series of experiments in vitro. We found that ALA_PDT can kill . Mechanistically, we found that ALA_PDT promoted ferroptosis-like death of , and the ROS scavenger N-Acetyl-L-cysteine (NAC) and ferroptosis inhibitor Ferrostatin-1 (Fer-1) can mitigate the ALA_PDT-mediated sterilization. Furthermore, ALA_PDT significantly up-regulated the transcription of heme oxygenase MAB_4773, increased the intracellular Fe concentration and altered the transcription of iron metabolism genes. ALA_PDT disrupted the integrity of the cell membrane and enhanced the permeability of the cell membrane, as evidenced by the boosted sterilization effect of antibiotics. In summary, ALA_PDT can kill via promoting the ferroptosis-like death and antibiotic sterilization through oxidative stress by changing iron metabolism. The study provided new mechanistic insights into the clinical efficacy of ALA_PDT against .
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox11030546