Fluoroquinolone resistance and mutational profile of gyrA gene in pulmonary MDR tuberculosis patients

Background Flouroquinolones (FQs) are the potential drugs that inhibit DNA synthesis and used in the treatment of MDR-TB and anti-TB short term regimens. In recent year’s high proportion of flouroquinolone (FQs) resistance in Mycobacterium tuberculosis isolates has been observed. The development of FQs resistance among multidrug resistant TB (Pre-XDR TB) negatively impact patient treatment outcome and is a serious threat to control TB. Methods A total of 562 samples were included in the study from patients with pulmonary TB which had been on anti-tuberculosis therapy. MTBDRsl assay was performed for molecular detection of mutations. Sequence analysis was performed for characterization and mutational profiling of FQ resistant isolates. Results FQs resistance was observed in 104 (18.5%) samples and most of them were previously treated and treatment failure cases. A total of 102 isolates had mutations in gyrA gene. While gyrB gene mutations were observed in only two isolates. Mutational analysis showed that the mutations mostly alter protein at codon 94 (D94G) (represents the replacement of aspartic acid with glycine) and 90 (A90V) (substitution of alanine with valine). In MDR and treatment failure cases, the FQs-R was most commonly associated with D94G mutation. Whereas, a high proportion of A90V mutation was observed in MTB isolates which were newly diagnosed. Conclusion The findings suggest that the genotypic studies for FQs resistance should be carried out at time of initial diagnosis, before starting treatment, to rule out all type of mutations and its potential use in the treatment and to control resistance.