ALA_PDT Promotes Ferroptosis-Like Death of <i>Mycobacterium abscessus</i> and Antibiotic Sterilization via Oxidative Stress
Xiaoyu Wang,
Meiyin Wan,
Lei Zhang,
Yongdong Dai,
Yang Hai,
Chenda Yue,
Junqi Xu,
Yadan Ding,
Mei Wang,
Jianping Xie,
Xia Lei,
Julia-Li Zhong
Affiliations
Xiaoyu Wang
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
Meiyin Wan
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
Lei Zhang
Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, College of Life and Sciences, Southwest University, Chongqing 400700, China
Yongdong Dai
Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, College of Life and Sciences, Southwest University, Chongqing 400700, China
Yang Hai
Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, College of Life and Sciences, Southwest University, Chongqing 400700, China
Chenda Yue
Department of Dermatology, Daping Hospital, The Army Medical University, Chongqing 400044, China
Junqi Xu
Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, College of Life and Sciences, Southwest University, Chongqing 400700, China
Yadan Ding
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
Mei Wang
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
Jianping Xie
Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, College of Life and Sciences, Southwest University, Chongqing 400700, China
Xia Lei
Department of Dermatology, Daping Hospital, The Army Medical University, Chongqing 400044, China
Julia-Li Zhong
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
Mycobacterium abscessus 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 M. abscessus infections, we conducted a series of experiments in vitro. We found that ALA_PDT can kill M. abscesses. Mechanistically, we found that ALA_PDT promoted ferroptosis-like death of M. abscesses, 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 Fe2+ concentration and altered the transcription of M. abscessus 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 M. abscesses 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 M. abscessus.
