Insights on efflux pumps and their implications in drug resistance and virulence.

Drug resistance in is assumed to be due to genetic alterations in the drug targets and reduced cell wall permeability. However, as observed in , drug resistance may also result from the overactivity of efflux systems, which is mostly unexplored. In this perspective, we discuss known efflux pumps involved in drug resistance and virulence and investigate similar regions in the genome of . analysis reveals that the major efflux pumps known to be associated with drug resistance and virulence have been retained during the reductive evolutionary process that underwent, e.g., RND superfamily, the ABC transporter BacA, and the MFS P55. However, some are absent (DinF, MATE) while others are derepressed (Mmr, SMR) in reflecting the specific environment where may live. The occurrence of several multidrug resistance efflux transporters shared between and reveals potential implications in drug resistance and virulence. The conservation of the described efflux systems in upon genome reduction indicates that these systems are potentially required for its intracellular survival and lifestyle. They potentially are involved in drug resistance, which could hamper leprosy treatment success. Studying efflux pumps as new drug targets is useful for future leprosy therapeutics, enhancing the global efforts to eradicate endemic leprosy, and prevent the emergence of drug resistance in afflicted countries.