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.
OBJECTIVE: The mechanisms of resistance to para-aminosalicylic acid (PAS) are undefined. In this study, we explored the mechanisms of M. tuberculosisPAS 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.
Authors: Claudio U Köser; Richard N Veerapen-Pierce; David K Summers; John A C Archer Journal: Antimicrob Agents Chemother Date: 2010-10 Impact factor: 5.191