Mutations in gyrA and gyrB among drug-resistant Mycobacterium tuberculosis isolates in South Korea

Abstract

Background: Group A fluoroquinolones (FLQs) are essential for treating multidrug-resistant tuberculosis (MDR-TB). Mutations in gyrA and gyrB cause FLQ resistance, but their patterns vary by region. This study evaluated FLQ-associated mutations in the gyrA and gyrB genes by analyzing minimum inhibitory concentrations (MICs) using 7H9 broth microdilution (BMD) and Löwenstein-Jensen phenotypic drug susceptibility test (L-J pDST).

Methods: A total of 304 isoniazid- and/or rifampicin-resistant isolates were analyzed. Genotypic drug susceptibility testing (gDST) was performed by sequencing gyrA (codons 74-113) and gyrB (codons 500-540). MICs for moxifloxacin (MFX) and levofloxacin (LFX) (0.0625-8.0 μg/mL) were determined using 7H9 BMD. Mutations were identified relative to the M. tuberculosis H37Rv reference. In L-J pDST, resistance breakpoints were 1.0 μg/mL for MFX and 2.0 μg/mL for LFX.

Results: Among isolates, 270 (88.81 %) were wild type and 34 (11.18 %) had mutations. D94G (44.82 %) and A90V (24.14 %) were the most frequent gyrA mutations. D500N (40 %) was the most common gyrB mutation. All gyrA mutants were MFX-resistant, while only 60 % of gyrB mutants were.

Conclusions: This study confirms gyrA mutations, especially D94G, as primary determinants of FLQ resistance in drug-resistant TB (including MDR-TB) in South Korea. gyrB mutations may also influence resistance. Combining gDST with phenotypic methods may improve resistance profiling.

Keywords: Drug-resistant gene; Fluoroquinolones; Mycobacterium tuberculosis; gyrA; gyrB.