ALA_PDT Promotes Ferroptosis-Like Death of <i>Mycobacterium abscessus</i> and Antibiotic Sterilization via Oxidative Stress

• Main Authors: Xiaoyu Wang (Author), Meiyin Wan (Author), Lei Zhang (Author), Yongdong Dai (Author), Yang Hai (Author), Chenda Yue (Author), Junqi Xu (Author), Yadan Ding (Author), Mei Wang (Author), Jianping Xie (Author), Xia Lei (Author), Julia-Li Zhong (Author)
• Format: Book
• Published: MDPI AG, 2022-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<i>Mycobacterium abscessus</i> 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 <i>M. abscessus</i> infections, we conducted a series of experiments in vitro. We found that ALA_PDT can kill <i>M. abscesses</i>. Mechanistically, we found that ALA_PDT promoted ferroptosis-like death of <i>M. abscesses</i>, 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 <i>M. abscessus</i> 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 <i>M. abscesses</i> 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 <i>M. abscessus</i>.

Item Description

10.3390/antiox11030546
2076-3921