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

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. The Ctrl, PDT1 and PDT2 bacteria were harvested for RNA preparation.RNA-seq is measured by Zhongke New Life (Shang Hai).(Ctrl: 0µg/mL ALA+0J/cm2 light, PDT1: 100µg/mL ALA+80J/cm2 light , PDT2: 100µg/mL ALA+160J/cm2 light)