What question did this study set out to answer?

The aim is to identify genetic mutations associated with drug resistance in Mycobacterium tuberculosis isolates from the Republic of Congo.

February 12, 2026Open Access

Molecular Characterization of Drug Resistance-Associated Mutations in Mycobacterium tuberculosis Isolates from the Republic of Congo Using Targeted Nanopore Sequencing

DADarrel Ornelle Elion AssianaLaboratoire National de Santé Publique du Congo LGLéa Gwladys GangoueLaboratoire National de Santé Publique du Congo FMFreisnel Hermeland MouzingaFondation Congolaise Pour La Recherche Médicale

Key Points

The aim is to identify genetic mutations associated with drug resistance in Mycobacterium tuberculosis isolates from the Republic of Congo.
Analyzed 45 culture-positive Mycobacterium tuberculosis isolates using targeted next-generation sequencing.
Identified resistance-related genes, including rpoB, katG, embB, gyrA, and rrs.
Characterized mutations linked to resistance for first and second-line injectable drugs.
48% of isolates showed at least one mutation related to drug resistance.
Rifampicin resistance was the most prevalent, found in 68.2% of resistant isolates.
Ethambutol resistance was noted in 50%, primarily linked to embB mutations.
Isoniazid resistance was identified in 40.9% of isolates, mainly associated with katG mutations.
Only 4.5% of isolates showed resistance to second-line injectable drugs.

Abstract

Tuberculosis (TB) remains a major public health challenge, particularly in sub-Saharan Africa, where the emergence of drug-resistant MTB undermines current control efforts. This study aimed to characterize genetic mutations associated with resistance to first- and second-line injectable drugs in MTB isolates from pulmonary TB patients in the Republic of Congo. A total of 45 culture-positive MTB isolates collected between 2018 and 2019 were analyzed using targeted next-generation sequencing on the MinION device. Resistance-associated genes, including rpoB, katG, embB, gyrA, and rrs, were examined. Overall, 22/45 isolates (48%) harbored at least one mutation associated with drug resistance. Among resistant isolates, rifampicin resistance was detected in 15 of 22 (68.2%), predominantly associated with mutations in the rpoB rifampicin resistance–determining region, including p.Ser531Leu, p.Asp516Val, and p.His526Tyr.Ethambutol resistance was observed in 11 of 22 isolates (50.0%) and was mainly associated with the embB p.Met306Val mutation. Isoniazid resistance was detected in 9 of 22 isolates (40.9%), primarily associated with the KatG p.Ser315Thr mutation. Fluoroquinolone resistance was identified in 2 of 22 isolates (9.1%), mainly associated with gyrA p.Ala90Val and p.Asp94Gly mutations. Resistance to second-line injectable drugs was detected in 1 of 22 isolates (4.5%) and was associated with the rrs p.Ala1401Gly mutation. These findings underscore the need to enhance molecular surveillance and strengthen treatment protocols for drug-resistant TB in the Republic of Congo to effectively combat this evolving health crisis.

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