PMID- 35326196 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220329 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 11 IP - 3 DP - 2022 Mar 14 TI - ALA_PDT Promotes Ferroptosis-Like Death of Mycobacterium abscessus and Antibiotic Sterilization via Oxidative Stress. LID - 10.3390/antiox11030546 [doi] LID - 546 AB - 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 Fe(2+) 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. FAU - Wang, Xiaoyu AU - Wang X AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China. AD - Department of Dermatology, Daping Hospital, The Army Medical University, Chongqing 400044, China. AD - 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. FAU - Wan, Meiyin AU - Wan M AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China. FAU - Zhang, Lei AU - Zhang L AD - 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. FAU - Dai, Yongdong AU - Dai Y AD - 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. FAU - Hai, Yang AU - Hai Y AD - 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. FAU - Yue, Chenda AU - Yue C AD - Department of Dermatology, Daping Hospital, The Army Medical University, Chongqing 400044, China. FAU - Xu, Junqi AU - Xu J AD - 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. FAU - Ding, Yadan AU - Ding Y AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China. FAU - Wang, Mei AU - Wang M AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China. FAU - Xie, Jianping AU - Xie J AD - 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. FAU - Lei, Xia AU - Lei X AD - Department of Dermatology, Daping Hospital, The Army Medical University, Chongqing 400044, China. FAU - Zhong, Julia-Li AU - Zhong JL AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China. LA - eng GR - 81773348/National Natural Science Foundation of China/ GR - 82072246/National Natural Science Foundation of China/ GR - 81871182/National Natural Science Foundation of China/ GR - 7820100597/2020 Chongqing Post-Doctoral Research Project Special Funding/ GR - ZK-2021-565/The Science and Technology Plan Project of Guizhou Province/ GR - 2018-5772-072/The Initial Research Funds for Ph.D in Zunyi Medical University/ GR - 2018-5772-066/2020 City-School Joint Project/ PT - Journal Article DEP - 20220314 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC8945036 OTO - NOTNLM OT - ALA_PDT OT - Mycobacterium abscessus OT - antibiotic resistance OT - ferroptosis OT - heme oxygenase MAB_4773 COIS- The authors declare that they have no conflict of interest. EDAT- 2022/03/26 06:00 MHDA- 2022/03/26 06:01 PMCR- 2022/03/14 CRDT- 2022/03/25 01:00 PHST- 2022/01/24 00:00 [received] PHST- 2022/03/06 00:00 [revised] PHST- 2022/03/11 00:00 [accepted] PHST- 2022/03/25 01:00 [entrez] PHST- 2022/03/26 06:00 [pubmed] PHST- 2022/03/26 06:01 [medline] PHST- 2022/03/14 00:00 [pmc-release] AID - antiox11030546 [pii] AID - antioxidants-11-00546 [pii] AID - 10.3390/antiox11030546 [doi] PST - epublish SO - Antioxidants (Basel). 2022 Mar 14;11(3):546. doi: 10.3390/antiox11030546.