Abstract: Objective  To study para-aminosalicylic acid (PAS) resistance rates in M. tuberculosis isolates and the relationship with thyA gene mutation.  Methods  Ninety-six M. tuberculosis strains were isolated and identified from the sputa or throat swab specimens of tuberculosis patients. M. tuberculosis strains resistance to PAS was determined by the proportional method, and their thyA gene mutation was detected by PCR-DNA sequencing.  Results  Of 96 M. tuberculosis isolates, 65 were PAS-sensitive, and 31 were PAS-resistant. Using M. tuberculosis H37Rv as a control, the thyA gene mutation rate in PAS-sensitive and PAS-resistant strains of M. tuberculosis were 46.15% (30/65) and 70.97% (22/31), respectively. Most of stains showed single base deletion and insertion mutations, in which C deletion at codon 19 and codon 168 were 54.84% (17/31), 25.81% (8/31) in PAS-resistant stains respectively, and 35.38% (23/65) and 12.31%(8/65) in PAS-sensitive strains respectively.  Conclusion  The frequency of the thyA gene mutation in PAS-resistant strains was significantly higher than that in PAS-sensitive strains. The thyA gene could be a potential target for the development of PAS resistance. But there were not any site with specific mutation found in this study.

Key words: Mycobacterium tuberculosis, p-Aminosalicyclic acid, Drug resistance, bacterial, Thymidylate synthase