Molecular characterization of para-aminosalicylic acid resistant Mycobacterium tuberculosis clinical isolates in southwestern China

Purpose: The aim of this study is to investigate para-aminosalicylic acid (PAS) resistance-related gene mutations in clinical Mycobacterium tuberculosis (MTB) isolates and analyze the associated risk factors in southwestern China.

Patients and methods: Total 122 PAS-resistant and 55 PAS-susceptible clinical isolates were obtained from Chongqing Public Health Medical Center between April 2014 and January 2018. Drug susceptibility test was performed, and the PAS resistance-related genes were sequenced.

Results: PAS-resistant strains were more likely to resist streptomycin (OR: 9.5, 95% CI: 3.87-23.3; P<0.01), isoniazid (OR: 5.98, 95% CI: 2.14-16.76; P<0.01), rifampin (OR: 5.01, 95% CI: 2.11-11.88; P<0.01), ethambutol (OR: 2.79, 95% CI: 1.44-5.4; P<0.01), levofloxacin (OR: 2.56, 95% CI: 1.33-4.93; P<0.01), and amikacin (OR: 4.29, 95% CI: 1.70-10.83; P<0.01). The sequencing results showed that 112 (91.8%) PAS-resistant strains harbored 30 different mutations in folC, thyA, and ribD. Mutations in folC were the most commonly observed in PAS-resistant isolates (54.5%, 61/112), followed by mutations in thyA and ribD. Residues I43 in folC, R235 in thyA, and ^-11G in upstream of ribD were hotspots for mutation sites.

Conclusion: PAS drug resistance in MTB in southwestern China is mainly caused by mutations in folC, thyA, and ribD, among which folC was the most frequent mutation. Some mutation hotspots exist in the three genes, which accounts for about 80% of total mutations. These results highlight the possibility of developing molecular diagnostic methods for PAS-resistant tuberculosis in the future.