Genetic mutations at rifampicin resistance-determining region of RpoB gene in conferring resistance to isolated multidrug-resistant tuberculosis strains

Introduction: Drug resistant tuberculosis (TB) among the new and retreatment cases was seen to be 5%. Multidrug resistant TB to at least isoniazid and Rifampicin is an alarming threat to the community and the scenario is even worse for retreatment cases showing rising trend over the years. A systematic analysis of the nature of the resistance conferred may contribute in understanding the common as well as rare genetic alterations that ultimately led to the genotypic resistance. The study thus involves a probe into the most common and rare patterns of genetic mutation that have led to the rifampicin resistance among the retreatment cases. The common and rare codons along with their change in amino acid sequences involved in conferring the resistance were looked for. Methods: The detection of the patterns genetic mutation is done by the Genotype MTBDR plus V2 kits (Hains Life Sciences) based on DNA strip technology (line probe assay). Results: The analysis has shown that only around 14.93% cases reflected exclusive mutations at around 531-533 region of the RpoB gene. Presence of both the wild and mutant gene segments simultaneously (WildType [WT] and MUT3) accounted to a striking percentage of 60.3% showing a heterogenous generation of susceptible and resistant strains at the same time. This pattern analysis showing maximum of heterogenous strains may be suggestive of capturing a generation under the process of conversion from WT to mutant type. About 95% reproducibility in liquid culture system further established the fact that most of the strains might be a cause for the rising attrition toward the first line of drugs. Conclusion: This pattern analysis showing maximum of heterogenous strains may be suggestive of capturing a generation under the process of conversion. The retrospective analysis showed how heterogenous population prevailed in the retreatment groups.