Investigation of Clofazimine Resistance and Genetic Mutations in Drug-Resistant <i>Mycobacterium tuberculosis</i> Isolates

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 <i>Mycobacterium tuberculosis&...

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Main Authors: Sanghee Park, Jihee Jung, Jiyeon Kim, Sang Bong Han, Sungweon Ryoo
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/11/7/1927
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author Sanghee Park
Jihee Jung
Jiyeon Kim
Sang Bong Han
Sungweon Ryoo
author_facet Sanghee Park
Jihee Jung
Jiyeon Kim
Sang Bong Han
Sungweon Ryoo
author_sort Sanghee Park
collection DOAJ
description 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 <i>Mycobacterium tuberculosis</i> (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.
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spelling doaj.art-5ea8528f0249478b858cb8064862b48f2023-11-30T23:28:47ZengMDPI AGJournal of Clinical Medicine2077-03832022-03-01117192710.3390/jcm11071927Investigation of Clofazimine Resistance and Genetic Mutations in Drug-Resistant <i>Mycobacterium tuberculosis</i> IsolatesSanghee Park0Jihee Jung1Jiyeon Kim2Sang Bong Han3Sungweon Ryoo4Clinical Research Center, Masan National Tuberculosis Hospital, Changwon-si 51755, KoreaClinical Research Center, Masan National Tuberculosis Hospital, Changwon-si 51755, KoreaClinical Research Center, Masan National Tuberculosis Hospital, Changwon-si 51755, KoreaDepartment of Laboratory Medicine, Masan National Tuberculosis Hospital, Changwon-si 51755, KoreaClinical Research Center, Masan National Tuberculosis Hospital, Changwon-si 51755, KoreaRecently, 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 <i>Mycobacterium tuberculosis</i> (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.https://www.mdpi.com/2077-0383/11/7/1927clofaziminemutationresistanceMDRXDRmycobacterium
spellingShingle Sanghee Park
Jihee Jung
Jiyeon Kim
Sang Bong Han
Sungweon Ryoo
Investigation of Clofazimine Resistance and Genetic Mutations in Drug-Resistant <i>Mycobacterium tuberculosis</i> Isolates
Journal of Clinical Medicine
clofazimine
mutation
resistance
MDR
XDR
mycobacterium
title Investigation of Clofazimine Resistance and Genetic Mutations in Drug-Resistant <i>Mycobacterium tuberculosis</i> Isolates
title_full Investigation of Clofazimine Resistance and Genetic Mutations in Drug-Resistant <i>Mycobacterium tuberculosis</i> Isolates
title_fullStr Investigation of Clofazimine Resistance and Genetic Mutations in Drug-Resistant <i>Mycobacterium tuberculosis</i> Isolates
title_full_unstemmed Investigation of Clofazimine Resistance and Genetic Mutations in Drug-Resistant <i>Mycobacterium tuberculosis</i> Isolates
title_short Investigation of Clofazimine Resistance and Genetic Mutations in Drug-Resistant <i>Mycobacterium tuberculosis</i> Isolates
title_sort investigation of clofazimine resistance and genetic mutations in drug resistant i mycobacterium tuberculosis i isolates
topic clofazimine
mutation
resistance
MDR
XDR
mycobacterium
url https://www.mdpi.com/2077-0383/11/7/1927
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AT jiyeonkim investigationofclofazimineresistanceandgeneticmutationsindrugresistantimycobacteriumtuberculosisiisolates
AT sangbonghan investigationofclofazimineresistanceandgeneticmutationsindrugresistantimycobacteriumtuberculosisiisolates
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