Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing

Abstract

<h2>ABSTRACT</h2><h3>Objectives</h3> Gatifloxacin (GAT), a fourth-generation fluoroquinolone (FQ), is used to treat drug-resistant tuberculosis. Although DNA gyrase mutations are the leading cause of FQ resistance, mutations conferring resistance to GAT remain inadequately characterized. <h3>Methods</h3> GAT-resistant mutants were selected from 7H10 agar plates containing 0.5 mg/L GAT (critical concentration). Mutations involved in GAT resistance were identified through whole-genome sequencing. <h3>Results</h3> In total, 123 isolates demonstrated resistance to GAT. Among these isolates, 55.3% (68/123) had <i>gyrA</i> gene mutations [G280A (D94N), A281G (D94G), G280T (D94Y) and G262T (G88C)]. The remainder (44.7%, 55/123) harboured <i>gyrB</i> gene mutations [A1495G (N499D), C1497A (N499K), C1497G (N499K) and A1503C (E501D)]. <h3>Conclusions</h3> Mutations in the <i>gyrA</i> and <i>gyrB</i> genes are the main mechanisms of GAT resistance. These findings provide new insight into GAT resistance, and contribute to molecular diagnosis of GAT resistance in the clinical setting.