title: [A preliminary study on the molecular characteristics of D-cycloserine resistance ofMycobacterium tuberculosis].
abstract: Objective:To investigate the relationship between D-cycloserine resistance and the gene mutations ofalrA,ddlAandcycAofMycobacterium(M.)tuberculosis, as well as the association between D-cycloserine resistance and spoligotyping genotyping.Methods:A total of 145M. tuberculosisstrains were selected from the strain bank. D-cycloserine resistant phenotypes of the strains were determined by the proportion method and the minimal inhibitory concentration was determined by resazurin microtiter assay. PCR amplification and DNA direct sequencing methods were used for the analysis of gene mutations. Relationship between the resistance phenotype and genotype was analyzed bychi-square test.Results:Of the 145 clinically collected strains, 24 (16.6%) of them were D-cycloserine resistant and 121 (83.4%) were sensitive. There were only synonymous mutations noticed onalrA,ddlAandcycAin sensitive strains. Of the 24 D-cycloserine resistant strains, 3 (12.5%) isolates'cycAand 1 (4.2%) isolates'alrAhappened to be non-synonymous mutations, in which the codes were 188, 318 and 508 ofcycA, and 261 ofalrA, respectively. Results on drug sensitivity tests confirmed the minimal inhibitory concentration of the mutant strains were all increased to some degrees. The D-cycloserine resistant rates of 88 Beijing genotype and 57 non-Beijing genotype strains were 20.5% and 10.5% , respectively, but with no statistically significant difference (χ(2) =2.47,P>0.05).Conclusions:The non-synonymous mutations ofalrAandcycAmight contribute to one of the mechanisms ofM. tuberculosisD-cycloserine resistance.M. tuberculosisBeijing genotype or non-Beijing genotype was not considered to be associated with the D-cycloserine resistance.
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: G L
authors.initials: GL
authors.lastname: Li
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Luo
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: S J
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: R B
authors.initials: RB
authors.lastname: Wang
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Lou
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: J X
authors.initials: JX
authors.lastname: Lyu
authors.affiliation: Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: K L
authors.initials: KL
authors.lastname: Wan
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology* / Q000627:therapeutic use; D000068476:Beijing; D003523:Cycloserine / Q000494:pharmacology* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D010641:Phenotype; D014376:Tuberculosis / Q000188:drug therapy*; D018088:Tuberculosis, Multidrug-Resistant
chemical_list: D000904:Antibiotics, Antitubercular; D003523:Cycloserine
keywords: Cycloserine; Drug resistance; Genes mutation; Mycobacterium tuberculosis