Frequency Determination of thyA Mutations and Prevalence of Resistance to Para- Aminosalycylic Acid in Clinical Strains of Drug- Resistant Mycobacterium Tuberculosis in Tehran from 2018 to 2021

The emergence of drug resistance and treatment- renitent Mycobacterium tuberculosis has made controlling the disease a challenge. World Health Organization (WHO) estimates that approximately 500,000 new cases of tuberculosis occur annually. Considering that mechanisms involved in drug resistance are yet to be elucidated and results of the studies are not consistent, we decided to investigate the correlation between mutations in thyA gene and resistance to para- aminosalicylic acid (PAS).

In this descriptive cross- sectional study, a total of 255 positive MTB specimens were isolated during a three- year period using standard microscopic and culture methods from which 68 Multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis samples were selected through drug susceptibility testing. Then, to determine potential mutations in thyA gene, the fragment was amplified using conventional PCR and products were sequenced. Afterward, mutations which have been induced amino acid substitutions were evaluated with various protein prediction tools. Also, the correlation between mutations and drug resistance was statistically determined using chi-square test.

From 255 clinical TB samples, 68 (26.7%, CI 21.3%) MDR / or XDR-TB strains were isolated. In total, 13 (19.1%) were PAS- resistant and 5 (38.4%) of them had different nucleotide mutations in thyA gene. All of the mutations were statistically correlated with drug resistance. Moreover, the results of bioinformatics showed that identified mutations could lead to the structural and functional disruption of the protein.

According to our results, mutations in thyA gene have appeared to be associated with resistance to PAS. Also, our findings have shed light on the potential of the analysis of short genomic regions and new computational tools in unraveling the molecular mechanisms of drug resistance.