Abstract
Multidrug resistant tuberculosis (MDR-TB) poses a serious global health concern. The development of drug-resistant mycobacterial strains is likely influenced by efflux transporters. In this study we created a deletion mutant of MSMEG_3118, a hypothetical efflux pump protein in Mycobacterium smegmatis, and characterized the mutant. It is shown that MSMEG_3118 acts as an efflux pump, and its deletion results in enhanced accumulation of the ethidium bromide. The MSMEG_3118 deletion mutant exhibited noticeable changes in colony morphology, slower growth rates, and reduced biofilm formation, indicating a larger role of this protein in mycobacterial physiology. Lipids profile showed elevated levels of menaquinone in the mutant. Interestingly, the mutant showed increased sensitivity to clofazimine and the proton motive force inhibitor CCCP but rendered higher resistance to several first- and second-line anti-tubercular drugs, such as rifampicin, isoniazid, streptomycin, vancomycin and erythromycin. All the changes in the mutant phenotypes were duly restored in the complemented mutant strain, suggesting a larger role of this protein in addition to an efflux pump transporter. Summarily, these results highlight a complex regulatory network that contributes to the multidrug resistance in mycobacteria.