An Arm-to-Disarm Strategy to Overcome Phenotypic AMR in .

Most front-line tuberculosis drugs are ineffective against hypoxic non-replicating drug-tolerant () contributing to phenotypic antimicrobial resistance (AMR). This is largely due to the poor permeability in the thick and waxy cell wall of persister cells, leading to diminished drug accumulation and reduced drug-target engagement. Here, using an "arm-to-disarm" prodrug approach, we demonstrate that non-replicating persisters can be sensitized to Moxifloxacin (MXF), a front-line TB drug.

"On demand" redox buffering by HS contributes to antibiotic resistance revealed by a bacteria-specific HS donor.

Understanding the mechanisms of antimicrobial resistance (AMR) will help launch a counter-offensive against human pathogens that threaten our ability to effectively treat common infections. Herein, we report bis(4-nitrobenzyl)sulfanes, which are activated by a bacterial enzyme to produce hydrogen sulfide (HS) gas. We found that HS helps maintain redox homeostasis and protects bacteria against antibiotic-triggered oxidative stress "on demand", through activation of alternate respiratory oxidases and cellular antioxidants.