Bedaquiline resistant Mycobacterium tuberculosis clinical isolates with and without rv0678 mutations have similar growth patterns under varying BDQ drug pressure

Abstract

Resistance associated mutations have been reported to alter the growth of Mycobacterium tuberculosis (MTB) isolates under drug pressure. However, there is little information on the growth characteristics of bedaquiline (BDQ) resistant isolates in the presence of BDQ. To further understand the role of rv0678, we aimed to study whether the presence of rv0678 variants in BDQ resistant isolates alters the killing effect of BDQ. We, therefore, selected BDQ resistant clinical MTB isolates with (n = 6) and without (n = 3) variants in rv0678 gene. Using time kill assays, growth inhibition; taken as the relative change in log average colony forming unit (CFU)/ml at selected time points (24–96 h), was studied at Minimum Inhibitory Concentrations (MICs): 0x, 1x, 2.5x, 5x, 7.5x, 10x for these isolates. Growth inhibition was then analyzed using Kruskal Wallis and Kolmogorov Smirnov tests in PRISM vr.9. During the 24–96 h lag phase isolates with and without variants in rv0678 showed a similar growth inhibition pattern. No difference was noted in growth inhibition between BDQ resistant isolates and H37Rv. These findings suggest that role of alternate mechanisms in contributing to BDQ tolerance needs to be explored.