The intrinsic antibiotic resistance to β-lactams, macrolides, and fluoroquinolones of mycobacteria is mediated by the whiB7 and tap genes

Abstract

The M. tuberculosis resistome includes a number of genes involved in intrinsic drug resistance. One of the major members of this system is the whiB7 gene encoding a transcription factor, which regulates expression of a number of genes—its regulon. In this study, we analyze the impact on intrinsic drug resistance levels of the whiB7 and tap genes and their prevalent mutants. The mutations found within whiB7 and tap genes in the genomes of strains belonging to Beijing and EAI-Manila lineages allowed us to investigate the new role of these genes in the intrinsic drug resistance of mycobacteria to β-lactams, fluoroquinolones, and macrolides and to assume their significance in the development of M. tuberculosis genotypes. Here we also established that the mutation in the tap gene–insC₅₈₁, previously described, as a marker of the Beijing lineage, cannot be the marker due to its absence in a number of Beijing strains.