Genetic Basis of Drug Resistance in Mycobacterium tuberculosis Strains from North Central Nigeria: A Molecular Epidemiology Study

Drug-resistant tuberculosis (DR-TB) poses a severe challenge to TB control programmes in Nigeria. Understanding the genetic basis of resistance through molecular characterisation of Mycobacterium tuberculosis strains is essential for designing effective treatment protocols. This study characterised drug resistance-conferring mutations in M. tuberculosis isolates from patients in North Central Nigeria, focusing on Benue and Plateau States. Culture-confirmed M. tuberculosis isolates were collected from 120 TB patients who failed standard first-line therapy. DNA extraction was followed by PCR amplification and Sanger sequencing of resistance-associated loci including rpoB (rifampicin resistance), katG and inhA (isoniazid resistance), embB (ethambutol), and gyrA (fluoroquinolone). Spoligotyping was used for lineage classification. Multidrug resistance (MDR-TB, defined as resistance to both rifampicin and isoniazid) was confirmed in 28 percent of isolates. The most common rpoB mutation was the Ser531Leu substitution. Beijing lineage strains were detected at a notable frequency, raising concerns about transmission of globally distributed MDR lineages. These results advocate for routine molecular drug susceptibility testing in North Central Nigeria and accelerated rollout of WHO-recommended rapid resistance diagnostics. Keywords: MDR-TB, rpoB gene, Mycobacterium tuberculosis, molecular epidemiology, North Central Nigeria