Examination of Genetic Mutations of Clofazimine Resistance in Drug-Resistant Mycobacterium TB Isolates

Anti-tuberculosis activity and resistance were recently refocused since clofazimine (CFZ) had a significant therapeutic benefit in treating multi-drug resistant tuberculosis (MDR-TB). We investigate the resistance of CFZ and genetic mutations in drug-resistant Mycobacterium tuberculosis strains to enhance the diagnosis and treatment of TB patients. CFZ range of CFZ was determined by testing 20 sensitive strains and 80 MDR clinical isolates. The correlation between the patients' treatment history and CFZ resistance was examined. PCR and DNA sequencing were employed to analyze mutations in the Rv0678, Rv1979c, and pepQ genes of CFZ-resistant and susceptible strains. Drug-resistant M. tuberculosis isolates had an 21.25% incidence of CFZ resistance with MIC > 1 mg/L. Neither bedaquiline nor CFZ therapy was the cause of CFZ resistance. It is necessary to perform a CFZ susceptibility test regardless of prior drug exposure. This study reported novel mutation sites associated with CFZ resistance in the pepQ (V85M/R437L/T438N and G605A/G619M/A610Q), Rv0678 (214 C→Tand 407T→C), and Rv1979c (155 A→C, 562 C→T, 1216G→A,724G→A, and 1057T→G) genes.