Whole-Genome Sequence Analysis to Assess Mutations in Efflux Pumps in Mycobacterium tuberculosis: The Influence in Drug Resistance

Efflux pumps are proteins related to the transport of molecules in bacteria, and some of them have been recently reported to be involved in drug resistance (DR) in Mycobacterium tuberculosis. In addition, the association with type 2 diabetes mellitus (T2DM) has been considered a factor favoring the development of drug resistance. Therefore, the aim of this study was to characterize, by analysis of M. tuberculosis genomes, the variants in efflux pump genes and to determine the level of association with T2DM and DR. Nearly 400 Mtb genomes from individuals with and without T2DM and with and without DR were recovered. Of the 164 efflux pump genes analyzed, 10 lack any variant, while 154 genes presented from 3 to 19 variants. The variant S217P in mmpL13a (Rv1145) was the most abundant, found in 98 (25%) isolates. A significant association was observed between 19 variants and DR, and between 20 variants and T2DM (p ≤ 0.005). Although preliminary, the results show a tendency for certain variants to appear in tuberculosis isolates from individuals with DR and T2DM, demonstrating the possible influence of the host in the evolution of tuberculosis. Further studies are necessary to confirm the participation of these variants in the efflux pump function in tuberculosis.