Putative MFS transporter Rv1250 of Mycobacterium tuberculosis is involved in multidrug efflux activity

Abstract

Drug-resistant Mycobacterium tuberculosis is one of the leading causes of global mortality. Mechanisms, such as slow uptake of drugs along with cell wall impermeability and active efflux, are some of the concerning reasons leading to drug resistance. Efflux pumps actively transport a wide variety of drugs and toxins away from the target site, which is considered an emerging cause for the failure of anti-tubercular medications and treatment. In this study, we report that the ability of Rv1250, a probable MFS-type transporter, influences the extrusion of multiple structurally unrelated classes of drugs, enhances the biofilm formation in E. coli and Mycobacterium smegmatis, and facilitates the survival of M. smegmatis cells inside the macrophage during antibiotic stress. Interestingly, in trans, the expression of rv1250 decreased the susceptibility of host cells to several structurally unrelated antibiotics, ranging from fluoroquinolones to aminoglycosides, beta-lactams, and anti-tubercular drugs, thus indicating its involvement in imparting intrinsic drug tolerance. In addition, the increased efflux of EtBr, norfloxacin, and Bocillin FL from host cells expressing rv1250 was revealed by the hosts ability to confer a lower level of antibiotic accumulation. Moreover, the expression of rv1250 resulted in the enhancement of biofilm formation. Overall, we conclude that Rv1250 of Mycobacterium tuberculosis might facilitate the survival of host cells under antimicrobial stress. One sentence summaryRole of Rv1250 as an efflux pump