Molecular characterization of multidrug-resistant Mycobacterium tuberculosis isolated from South-central in China

Abstract

Rifampicin (RIF) and isoniazid (INH) Mycobacterium tuberculosis isolates were characterized from south-central China and transmission patterns within the Beijing genotype were detected in multidrug-resistant isolates. Six genetic regions, including rpoB for RIF, and katG, inhA, ahpC, mabA-inhA promoter and oxyR-ahpC intergenic region for INH were analyzed by DNA sequencing in 60 multidrug-resistant isolates, including 7 extensively drug-resistant isolates. The genomic deletion RD105 was characterized by genotyping. The results showed that 91.7% of MDR isolates carried mutations in the rpoB gene and 85.0% of the MDR isolates had at least one mutation in the INH resistance-associated loci detected. In total, these six genetic regions are responsible for 95.0% of MDR isolates. Mutations in the XDR isolates were focused on rpoB 531 or rpoB 526, and katG 315, correlating to a higher frequency level of resistance to RIF MIC ⩾8 μg ml⁻¹ and INH MIC ⩾4 μg m⁻¹. Three novel katG mutants (G273S, I266T and P232S) and three new alleles (E458A, S509R and P535S) in the rpoB gene were identified. Among the 85 clinical isolates, 78 are Beijing genotypes and the other 7 are non-Beijing genotypes. The results present the identification of genetic markers in M. tuberculosis isolates, some of which may be unique to this particular geographic niche. An understanding of the mutations in these drug-resistant strains may aid in choosing the appropriate chemotherapy regimens on the pharmacogenetic properties of the mutations for the prevention and control of tuberculosis.

Prevalence and Molecular Characteristics of Drug-Resistant Mycobacterium tuberculosis in Hunan, China

“…DNA sequencing of the hot spot regions in genetic loci demonstrated that the frequency of mutations occurring among INHresistant isolates was 78.7%, similar to the results reported in Jiangxi (19) but lower than the data from Fujian and Shanghai, China. For the RIF-resistant isolates in China, substantial proportions (90.2% to 97.2%) of mutations within the rpoB gene were observed (19)(20)(21)(22)(23)(24)(25). Our results showed that 87.0% of the RIF-resistant isolates carried mutations in the rpoB gene.…”

Compensatory Mutations of Rifampin Resistance Are Associated with Transmission of Multidrug-Resistant Mycobacterium tuberculosis Beijing Genotype Strains in China

“…RIF targets the ␤ subunit of the RNA polymerase, encoded by the rpoB gene, and M. tuberculosis can acquire resistance to RIF through mutations in this gene, especially in the 81-bp RIF resistance-determining region (RRDR) (10)(11)(12). Gagneux et al (13) found that the acquisition of RIF resistance in laboratory-derived strains is usually accompanied by a fitness cost.…”

Identification and Characterization of Non-Tuberculous Mycobacteria Isolated from Tuberculosis Suspects in Southern-Central China

“…AFB were then cultured in p-nitrobenzoic acid (PNB) and thiophene-2-carboxylic acid hydrazide (TCH) modified L-J medium [11] . Isolates that could grow in both PNB and TCH modified L-J medium were considered as NTM, which were subsequently genotyped by 16S rRNA gene and ITS sequencing.…”