Role of mutations in dihydrofolate reductase DfrA (Rv2763c) and thymidylate synthase ThyA (Rv2764c) in Mycobacterium tuberculosis drug resistance

C.U. Köser, R.N. Veerapen-Pierce, D.K. Summers, J.A. Archer
Antimicrob Agents Chemother, 54(10), pp. 4522-4523, (2010)

Role of mutations in dihydrofolate reductase DfrA (Rv2763c) and thymidylate synthase ThyA (Rv2764c) in Mycobacterium tuberculosis drug resistance

Keywords

Dihydrofolate reductase DfrA (Rv2763c), Thymidylate synthase ThyA

Abstract

​We would like to comment on a number of recent reports in this journal (6, 8, 12, 18) concerning Mycobacterium tuberculosis dihydrofolate reductase (DHFR), encoded by dfrA (Rv2763c). Around 36% of phenotypically para-aminosalicylic acid (PAS)-resistant M. tuberculosis strains harbor mutations in thyA (Rv2764c), which encodes a thymidylate synthase (20). In their effort to elucidate the remaining unknown resistance mechanism(s), Mathys et al. extended their sequence analysis to a number of additional genes, including dfrA (12). It was unclear whether the three dfrA mutations they identified in the PAS-resistant strains P-693 and P-3158 could contribute to PAS resistance on their own. Nonetheless, these findings are notable for two reasons.

Code

DOI: 10.1128/AAC.00422-10

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