Characterization of drug resistance-associated mutations among clinical multidrug-resistant Mycobacterium tuberculosis isolates from Hebei Province, China.

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Characterization of drug resistance-associated mutations among clinical multidrug-resistant Mycobacterium tuberculosis isolates from Hebei Province, China.

J Glob Antimicrob Resist. 2019 Mar 26;:

Authors: Li Q, Wang Y, Li Y, Gao H, Zhang Z, Feng F, Dai E

Abstract
BACKGROUND: Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is considered one of the major public health problems and a social burden in China. There is little information on the molecular characterization of clinical MDR-TB isolates in the Hebei Province of China.
METHODS: We identified 123 MDR-TB strains in sputum cultures using traditional drug sensitivity tests. We isolated the strains and tested them for mutations in seven genes associated with resistance to four drugs: katG and inhA promoter for isoniazid (INH), rpoB for rifampicin (RFP), gyrA and gyrB for ofloxacin (OFLX), rrs and eis promoter for kanamycin (KAN). All strains were genotyped by spoligotyping and mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) analysis at 15-loci.
RESULTS: We found 39 distinct mutations at the seven loci in 114 clinical isolates, accounting for 92.6% of the 123 MDR strains tested. The frequencies of INH, RFP, OFLX and KAN resistance-associated mutations were 82.1% (101/123), 83.7% (103/123), 92.1% (35/38) and 76.2% (16/21), respectively, in the MDR strains. The most prevalent mutations involved in resistance against INH were Ser315Thr in katG (70/123, 56.9%) and C-15 T in inhA (15/123,12.2%); against RFP Ser531Leu in rpoB (72/123,58.5%); against OFLX Asp94Gly in gyrA (10/38,26.3%); and against KAN, A1401 G in rrs (12/21,57.1%). Four novel gyrB mutants (Asn99The, Leu442Leu, Ser447Phe, and Ala504Val) were identified. Mutations in katG, rpoB, (or both) and inhA promoter, exhibited a sensitivity of 75.6% and a specificity of 97.0% for detection of MDR-TB.DNA sequencing of the seven loci in this study was 57.1% sensitive and 91.0% specific for the prediction of XDR-TB isolates.
CONCLUSIONS: These results may be one of value in the rapid molecular detection of MDR and XDR strains in clinical samples in Hebei Province.

PMID: 30926465 [PubMed - as supplied by publisher]