title: 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.
authors: 1] School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China [2] Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Xiao-li
authors: XL
authors: Yu
authors: 1] School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China [2] Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Zi-lu
authors: ZL
authors: Wen
authors: School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China.
authors: Gao-zhan
authors: GZ
authors: Chen
authors: School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China.
authors: Rui
authors: R
authors: Li
authors: School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China.
authors: Bing-bing
authors: BB
authors: Ding
authors: Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Yu-feng
authors: YF
authors: Yao
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai, China.
authors: Yao
authors: Y
authors: Li
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai, China.
authors: Hai
authors: H
authors: Wu
authors: Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Xiao-kui
authors: XK
authors: Guo
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai, China.
authors: Hong-hai
authors: HH
authors: Wang
authors: Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Shu-lin
authors: SL
authors: Zhang
mesh_terms: D000046:Academic Medical Centers; D000483:Alleles; D019943:Amino Acid Substitution; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002374:Catalase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002681:China / Q000453:epidemiology; D021901:DNA, Intergenic; D012321:DNA-Directed RNA Polymerases; D024901:Drug Resistance, Multiple, Bacterial; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D021901:DNA, Intergenic; C505805:rpoB protein, Mycobacterium tuberculosis; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D007538:Isoniazid; D012293:Rifampin