[Mutations in the thymidylate synthase gene is a major mechanism in the para-aminosalicylic acid resistance of M. tuberculosis].
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.
Zhang
Zong-de
ZD
Department of Molecular Biology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Zhao
Yan-Lin
YL
Li
Zi-Hui
ZH
Jia
Hong-Yan
HY
Liu
Yu-Hong
YH
Chen
Xi
X
Liu
Zhong-Quan
ZQ
Du
Bo-Ping
BP
Xing
Ai-Ying
AY
Ma
Yu
Y
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*
D000995:Antitubercular Agents; D010131:Aminosalicylic Acid; D013940:Thymidylate Synthase