A biofilm activator MmtA1 modulates multi-drug resistance in mycobacteria

Abstract When exposed to the antibiotic-induced stress, Mycobacterium species have the ability to survive by forming protective multicellular structures known as biofilms. However, the underlying mechanism of biofilm formation in response to antibiotics is not fully understood. In this study, we identified a transcriptional factor, MmtA1, which responds to the first-line anti-tuberculosis drug isoniazid and regulates genes involved in sugar and lipid transportation. This leads to increased biofilm formation and multi-drug resistance in M. smegmatis. These findings suggest that isoniazid may act as a molecular messenger, working in coordination with transcriptional regulatory factors to induce multidrug resistance under chemotherapy. Importance This study elucidates a novel transcriptional regulatory mechanism by which Mycobacterium smegmatis develops multidrug resistance in response to the anti-tuberculosis drug isoniazid. By linking antibiotic stress to transcriptional regulation and metabolic adaptation, this work provides new insights into drug-induced tolerance in mycobacteria, suggesting antibiotic functional as inducer of biofilm formation, triggering a coordinated transcriptional response to enhance bacterial survival under antibiotic pressure.