Therapeutic potential of Bacillus sonorensis PMC204 membrane vesicles against drug-resistant Mycobacterium tuberculosis.

Tuberculosis remains a severe global health threat, exacerbated by the rising prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis. Despite the urgent need for effective interventions, the development of anti-tuberculosis drugs has been slow, and the emergence of pan-drug-resistant strains underscores the critical need for innovative therapeutic strategies. This study introduces Bacillus sonorensis PMC204, a novel probiotic strain with potent anti-tuberculosis properties identified through extensive screening. PMC204 significantly reduced M. tuberculosis H37Rv and XDR strains within Raw 264.7 macrophage cells. Moreover, membrane vesicles (MVs) derived from this strain exhibited superior inhibitory effects against both standard and XDR strains of M. tuberculosis. Proteomic analysis of the isolated MVs revealed a high abundance of flagellin proteins, which are hypothesized to play a pivotal role in the observed anti-tuberculosis effects. These findings also suggest a close link between the therapeutic efficacy of PMC204 and autophagy activation. Safety assessments further demonstrated the feasibility of PMC204 as a potential anti-tuberculosis therapeutic. The anti-tuberculosis activity of bacterial MVs represents an innovative approach in microbiome therapeutics, positioning PMC204 as a next-generation probiotic distinct from conventional strains. This study contributes to advancing the field of microbiome-based therapeutics and presents promising avenues for managing drug-resistant tuberculosis.