Molecular analysis of genetic mutations among cross-resistant second-line injectable drugs reveals a new resistant mutation in Mycobacterium tuberculosis

• Published in: Diagnostic microbiology and infectious disease 2016-08, Vol.85 (4), p.433-437
• Main Authors: Malinga, Lesibana, Brand, Jeannette, Olorunju, Steve, Stoltz, Anton, van der Walt, Martie
• Format: Article
• Language: English
• Subjects: Antitubercular Agents - pharmacology; Cross-resistance; DNA Mutational Analysis; G878A mutation; Genes, Bacterial; Infectious Disease; Injections; Internal Medicine; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Point Mutation; rrs gene; Second-line injectable drugs
• ISSN: 0732-8893; 1879-0070
• DOI: 10.1016/j.diagmicrobio.2016.05.010

Abstract Mutations causing mono and cross-resistance among amikacin, kanamycin and capreomycin of second-line injectable drugs (SLIDs) namely are not well understood. We investigated 124 isolates of Mycobacterium tuberculosis for mutations within rrs , eis, tlyA and efflux pump (Rv1258c and Rv0194) genes involved in resistance towards SLIDs. The distribution of mutations across these genes were significantly different in strains with mono-resistance or cross-resistance. A new mutation G878A was found in rrs gene, among strains with capreomycin mono-resistant, or in strains with cross-resistance of capreomycin, kanamycin and amikacin. This mutation was associated with the Euro-American X3 lineage ( P < 0.0001). Mutations in the two efflux genes Rv1258c and Rv0194 were confined to strains with only capreomycin/amikacin/kanamycin cross-resistance. We further investigated the minimum inhibitory concentration of capreomycin on isolates with new G878A mutation ranging from 8 μg/mL to 64 μg/mL. Inclusion of G878A on new molecular assays could increase the sensitivity of capreomycin resistance detection.