Whole-Genome and Targeted Sequencing of 75 Drug-ResistantClinical Isolates in South Korea.

BACKGROUND: Tuberculosis (TB), an infectious disease caused by(), remains a major public health concern, particularly because of the increasing incidence of drug-resistant TB. In Republic of Korea, research on genes related to TB resistance is limited; therefore, in this study, we identified resistance-associated mutations in TB clinical isolates from Republic of Korea.

METHODS: We evaluated and compared phenotypic drug susceptibility testing (pDST) and genotypic drug susceptibility testing (gDST) using whole-genome sequencing (WGS) and targeted sequencing in 75 clinicalisolates collected in Republic of Korea between 2005 and 2009. Specifically, we analyzed mutations associated with resistance against isoniazid (INH), rifampicin (RIF), moxifloxacin (MFX), pyrazinamide (PZA), pretomanid (PMD), delamanid (DLM), linezolid (LZD), and bedaquiline (BDQ) and compared them with those in the 2023 WHO mutation catalog.

RESULTS: We detected resistance-associated mutations in 98.7% of INH- and RIF-resistant isolates, with a high degree of concordance between the pDST and gDST results for most drugs. However, PZA results were discrepant for 16 isolates.

CONCLUSIONS: Our findings highlight the potential of WGS and targeted sequencing as powerful tools for diagnosing TB drug resistance and emphasize the need for further validation before their routine implementation in clinical settings.