title: Characterization of mutations in streptomycin-resistant Mycobacterium tuberculosis isolates in Sichuan, China and the association between Beijing-lineage and dual-mutation in gidB.
abstract: Mutations in rpsL, rrs, and gidB are well linked to streptomycin (STR) resistance, some of which are suggested to be potentially associated with Mycobacterium tuberculosis genotypic lineages in certain geographic regions. In this study, we aimed to investigate the mutation characteristics of streptomycin resistance and the relationship between the polymorphism of drug-resistant genes and the lineage of M. tuberculosis isolates in Sichuan, China. A total of 227 M. tuberculosis clinical isolates, including 180 STR-resistant and 47 pan-susceptible isolates, were analyzed for presence of mutations in the rpsL, rrs and gidB loci. Mutation K43R in rpsL was strongly associated with high-level streptomycin resistance (P < 0.01), while mutations in rrs and gidB potentially contributed to low-level resistance (P < 0.05). No general association was exhibited between STR resistance and Beijing genotype, however, in STR-resistant strains, Beijing genotype was significantly correlated with high-level STR resistance, as well as the rpsL mutation K43R (P < 0.01), indicating that Beijing genotype has an evolutionary advantage under streptomycin pressure. Notably, in all isolates of Beijing genotype, a dual mutation E92D (a276c) and A205A (a615g) in gidB was detected, suggesting a highly significant association between this dual mutation and Beijing genotype.
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of The Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, PR China.
authors.forename: Honghu
authors.initials: H
authors.lastname: Sun
authors.affiliation: Chengdu Center for Food and Drug Control, Chengdu, Sichuan 610000, PR China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of The Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of The Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Pi
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of The Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of The Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of The Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Tropical Bioscience and Biotechnology, CATAS, Haikou, Hainan 571101, PR China.
authors.forename: Yuding
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Public Health, Chengdu Medical College, Chengdu, Sichuan 610500, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: Public Health Clinical Center of Chengdu, Chengdu, Sichuan 610000, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Luo
authors.affiliation: WHO Supranational TB Reference Laboratory, Institut Pasteur de la Guadeloupe, Abymes 97183, Guadeloupe, France.
authors.forename: Nalin
authors.initials: N
authors.lastname: Rastogi
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610064, PR China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of The Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, PR China. Electronic address: qunsun@scu.edu.cn.
authors.forename: Qun
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D002681:China; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D010641:Phenotype; D013183:Sputum / Q000382:microbiology; D013307:Streptomycin / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial; D013307:Streptomycin
keywords: Beijing lineage; Dual-mutation; Mycobacterium tuberculosis; Streptomycin resistance