Abstract
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.
Highlights
Mycobacterial infections can be divided into three main categories: (1) infections caused by Mycobacterium tuberculosis or M. bovis, (2) infections caused by M. leprae, and (3) non-tuberculous mycobacteria (NTM) infection [1]
The results demonstrated that Aminolevulinic acid photodynamic therapy (ALA_PDT) could kill on the1.growth of M.can abscesses
The results demonstrated that ALA_PDT promoted M. abscessus ferroptosis‐like death, demonstrated that ALA_PDT promoted M. abscessus ferroptosis-like death, via 2+
Summary
Mycobacterial infections can be divided into three main categories: (1) infections caused by Mycobacterium tuberculosis or M. bovis, (2) infections caused by M. leprae, and (3) non-tuberculous mycobacteria (NTM) infection [1]. NTMs are diverse and ubiquitous in the environment, but only very few can cause serious infections, such as M. abscesses [2]. As an emerging pathogen worldwide, M. abscesses is a rapidly growing NTM [3]. M. abscesses is resistant to most anti-tuberculosis drugs, such as macrolides, aminoglycosides, rifampicin, tetracycline and β-lactam antibiotics [1]. Multi-drug resistant M. abscessus was developed via mechanisms similar to other NTMs [4], and greatly limited the choice of antibiotics. New measures against multi-drug resistant M. abscesses are intensively pursued, such as phage therapy [5,6], natural or synthetic antimicrobial peptide [7] and photodynamic
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