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ALA_PDT promotes the ferroptosis-like death of Mycobacterium abscessus and antibiotic sterilization via oxidative stress

ABSTRACT: Mycobacterium abscessus is one of the common clinical non-tuberculous mycobacteria (NTM) which can cause severe skin infections. 5-Aminolevulinic acid photodynamic therapy (ALA_PDT) is an emerming effective antimicrobial medication. To explore whether ALA_PDT can treat M. abscessus infections, we found that ALA_PDT can kill M. abscesses via colony forming unit method. ALA_PDT promoted ferroptosis-like death of M. abscesses, and the antioxidant 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, altering 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. This new mechanism of ALA_PDT against M. abscessus might underlie its clinical efficacy.

ORGANISM(S): Mycobacteroides abscessus

PROVIDER: GSE193092 | GEO | 2022/03/30

REPOSITORIES: GEO

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