[Mutations in the Thymidylate Synthase Gene Is a Major Mechanism in the Para-Aminosalicylic Acid Resistance of M. Tuberculosis]

Zhonghua Jie He He Hu Xi Za Zhi. 2007 Sep;30(9):683-5.
[Article in Chinese]

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.

Method: 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.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminosalicylic Acid / pharmacology*
  • Antitubercular Agents / pharmacology*
  • Drug Resistance, Bacterial / genetics*
  • Genes, Bacterial
  • Mutation
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / genetics*
  • Thymidylate Synthase / genetics*

Substances

  • Antitubercular Agents
  • Aminosalicylic Acid
  • Thymidylate Synthase