Mycobacterium tuberculosis Adaptation in Response to Isoniazid Treatment in a Multi-Stress System That Mimics the Host Environment

Isoniazid (INH) is an antibiotic that is widely used to treat tuberculosis (TB). Adaptation to environmental stress is a survival strategy for Mycobacterium tuberculosis and is associated with antibiotic resistance development. Here, mycobacterial adaptation following INH treatment was studied using a multi-stress system (MS), which mimics host-derived stress. Mtb H37Rv (drugsusceptible), mono-isoniazid resistant (INH-R), mono-rifampicin resistant (RIF-R), and multidrugresistant (MDR) strains were cultivated in the MS with or without INH. The expression of stressresponse genes (hspX, tgs1, icl1, and sigE) and lipoarabinomannan (LAM)-related genes (pimB, mptA, mptC, dprE1, dprE2, and embC), which play important roles in the host-pathogen interaction, were measured using real-time PCR. The different adaptations of the drug-resistant (DR) and drugsusceptible (DS) strains were presented in this work. icl1 and dprE1 were up-regulated in the DR strains in the MS, implying their roles as markers of virulence and potential drug targets. In the presence of INH, hspX, tgs1, and sigE were up-regulated in the INH-R and RIF-R strains, while icl1 and LAM-related genes were up-regulated in the H37Rv strain. This study demonstrates the complexity of mycobacterial adaptation through stress response regulation and LAM expression in response to INH under the MS, which could potentially be applied for TB treatment and monitoring in the future.

Automated summary

This study investigated the adaptive responses of Mycobacterium tuberculosis to isoniazid treatment using a multi-stress system. The expression of stressresponse and lipoarabinomannan-related genes were measured, revealing different adaptations between drug-resistant and drug-susceptible strains. The study demonstrates the complexity of mycobacterial adaptation and provides potential applications for tuberculosis treatment and monitoring in the future.