Mycobacterium tuberculosis rrs A1401G mutation correlates with high-level resistance to kanamycin, amikacin, and capreomycin in clinical isolates from mainland China.
Mutations correlating phenotypic resistance level with the injectable second-line anti-tuberculosis drugs (SLDs) including kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) remain elusive. A collection of 114 Mycobacterium tuberculosis clinical isolates from mainland China was analyzed. The minimum inhibitory concentration (MIC) of each strain was determined and the sequences of rrs, tlyA, promoter of eis as well as 5' untranslated region (UTR) of whiB7 were amplified and sequenced. No mutation in tlyA, promoter of eis and 5' UTR of whiB7, was found to be associated with resistance among these samples. Sequencing data of 1400 rrs region demonstrated the A1401G mutation in rrs was prevalent, which presented in 84% of the KAN resistant isolates while only in about 50% of the AMK or CAP resistant isolates. Furthermore, most of the resistant isolates with A1401G mutation showed high-level resistance to these injectable SLDs. In conclusion, our results suggest the rrs A1401G mutation was related to high-level resistance to KAN, AMK, and CAP in M. tuberculosis isolates from mainland China.
Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
Qinglin
Q
Du
Guangming
G
Dai
Quanxin
Q
Long
Xia
X
Yu
Lingling
L
Dong
Hairong
H
Huang
Jianping
J
Xie
D000583:Amikacin / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology*; D002207:Capreomycin / Q000494:pharmacology; D002681:China; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D007612:Kanamycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D014376:Tuberculosis / Q000382:microbiology*
D000995:Antitubercular Agents; D012336:RNA, Ribosomal, 16S; D002207:Capreomycin; D007612:Kanamycin; D000583:Amikacin
Amikacin; Capreomycin; Kanamycin; Mycobacterium tuberculosis; rrs A1401G