Investigation of Clofazimine Resistance and Genetic Mutations in Drug-Resistant Mycobacterium tuberculosis Isolates.
Sanghee ParkJihee JungJiyeon KimSang Bong HanSung-Weon RyooPublished in: Journal of clinical medicine (2022)
Recently, as clofazimine (CFZ) showed a good therapeutic effect in treating multi-drug-resistant tuberculosis (MDR-TB), the anti-tuberculosis activity and resistance were re-focused. Here, we investigated the CFZ resistance and genetic mutations of drug-resistant Mycobacterium tuberculosis (DR-Mtb) isolates to improve the diagnosis and treatment of drug-resistant TB patients. The minimal inhibitory concentration (MIC) of CFZ was examined by resazurin microtiter assay (REMA) with two reference strains and 122 clinical isolates from Korea. The cause of CFZ resistance was investigated in relation to the therapeutic history of patients. Mutations of Rv0678, Rv1979c and pepQ of CFZ resistant isolates were analyzed by PCR and DNA sequencing. The rate of CFZ resistance with MIC > 1 mg/L was 4.1% in drug-resistant Mtb isolates. The cause of CFZ resistance was not related to treatment with CFZ or bedaquiline. A CFZ susceptibility test should be conducted regardless of dugs use history. The four novel mutation sites were identified in the Rv0678 and pepQ genes related to CFZ resistance in this study.
Keyphrases
- drug resistant
- mycobacterium tuberculosis
- multidrug resistant
- acinetobacter baumannii
- pulmonary tuberculosis
- end stage renal disease
- ejection fraction
- newly diagnosed
- genome wide
- gene expression
- prognostic factors
- peritoneal dialysis
- escherichia coli
- genetic diversity
- high throughput
- patient reported outcomes
- single cell
- emergency department
- single molecule
- copy number
- mass spectrometry
- antiretroviral therapy
- drug induced