[Multidimensional characterization of biofilm formation promoted by Mycobacterium tuberculosis Rv1904]

Mycobacterium tuberculosis (M. tb), the causative agent of tuberculosis, forms biofilms that contribute significantly to enhanced drug resistance. This study aimed to investigate the role of Rv1904 in the biofilm formation of M. tb. Recombinant strains were constructed for both Mycobacterium smegmatis and M. tb, followed by systematic biological characterization in terms of colony morphology, biofilm-forming ability, sliding motility and aggregation phenotypes, transcription levels of specific genes, tolerance to environmental stresses, intracellular survival capacity, and susceptibility to multiple compounds. The results demonstrated that Rv1904 markedly promoted biofilm formation, upregulated the transcription of the fatty acid synthesis gene fabg4, and enhanced bacterial tolerance to abiotic stresses such as temperature fluctuations, oxidative damage, and nutrient deprivation. These effects collectively improved intracellular survival within host cells. Among the seven tested compounds, thioacetazone (TB1) exhibited the strongest inhibitory effect on biofilm formation. In conclusion, Rv1904 enhances the environmental adaptation and survival advantage of M. tb by promoting biofilm formation, whereas TB1 effectively suppresses Rv1904-mediated biofilm formation. This study reveals the critical role of Rv1904 in biofilm regulation and provides a potential new target for the development of anti-tuberculosis drugs targeting biofilms.