Affiliation:
1. Division of Bacterial Disease Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea
2. Clinical Research Center, Masan National Tuberculosis Hospital, Changwon-si 51755, Republic of Korea
Abstract
Rapid and accurate detection of tuberculosis (TB) drug resistance is critical for the successful treatment and control of TB. Here, we investigated resistance to anti-TB drugs and genetic variations in 215 drug-resistant Mycobacterium tuberculosis isolates in Korea. Genetic variations were observed in rpoB Ser531Leu, katG Ser315Thr, and gyrA Asp94Gly; however, the minimum inhibitory concentrations varied, which can be attributed to other resistance mechanisms. Examination of genetic relatedness among drug-resistant isolates revealed that the cluster size of resistant bacteria was less than six strains, suggesting no evidence of a large-scale epidemic caused by a specific strain. However, rpoC mutants of the rifampicin-resistant isolates were composed of five types of clusters, suggesting that these compensatory mutations advance propagation. In the present study, more than 90% of the resistance mechanisms to major anti-TB drugs were identified, and the effect of each mutation on drug resistance was estimated. With the clinical application of recent next-generation sequencing-based susceptibility testing, the present study is expected to improve the clinical utilization of genotype-based drug susceptibility testing for the diagnosis and treatment of patients with drug-resistant TB.
Funder
Korea National Institute of Health
Subject
Pharmacology (medical),Infectious Diseases,Microbiology (medical),General Pharmacology, Toxicology and Pharmaceutics,Biochemistry,Microbiology