title: [Mutations in the thymidylate synthase gene is a major mechanism in the para-aminosalicylic acid resistance of M. tuberculosis].
abstract: OBJECTIVE
  The mechanisms of resistance to para-aminosalicylic acid (PAS) are undefined. In this study, we explored the mechanisms of M. tuberculosis PAS resistance in clinical isolates.
  
  
  METHODS
  The whole sequence of thymidylate synthase (thyA) gene encoding thyA genes was sequenced in 51 para-aminosalicylic acid (PAS)-sensitive and 44 resistant M. tuberculosis clinical isolates.
  
  
  RESULTS
  Sixteen of 44 resistant M. tuberculosis clinical isolates had mutations in the thyA genes, a mutation rate of 36.4% (16/44). No mutations were detected in the sensitive clinical isolates. The mutation types included substitutions, conversions and deletions.
  
  
  CONCLUSIONS
  Mutations in the thyA gene is associated with PAS resistance in M. tuberculosis clinical isolates, and mutations in thyA gene probably represent a major mechanism of developing resistance to the drug. Thymidylate synthase is likely to be the target of PAS action.
authors: Department of Molecular Biology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
authors: Zong-de
authors: ZD
authors: Zhang
authors: Yan-Lin
authors: YL
authors: Zhao
authors: Zi-Hui
authors: ZH
authors: Li
authors: Hong-Yan
authors: HY
authors: Jia
authors: Yu-Hong
authors: YH
authors: Liu
authors: Xi
authors: X
authors: Chen
authors: Zhong-Quan
authors: ZQ
authors: Liu
authors: Bo-Ping
authors: BP
authors: Du
authors: Ai-Ying
authors: AY
authors: Xing
authors: Yu
authors: Y
authors: Ma
mesh_terms: D010131:Aminosalicylic Acid / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D010131:Aminosalicylic Acid; D013940:Thymidylate Synthase