rpoB Mutations and Effects on Rifampin Resistance in Mycobacterium tuberculosis

To investigate the mutations within the whole gene of and analyze their effects on rifampin (RIF) resistance based on crystal structure. We sequenced the entire gene in 175 tuberculosis isolates and quantified their minimum inhibitory concentrations using microplate-based assays. Additionally, the s...

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Bibliographic Details
Published inInfection and drug resistance Vol. 14; pp. 4119 - 4128
Main Authors Li, Ma-chao, Lu, Jie, Lu, Yao, Xiao, Tong-yang, Liu, Hai-can, Lin, Shi-qiang, Xu, Da, Li, Gui-lian, Zhao, Xiu-qin, Liu, Zhi-guang, Zhao, Li-li, Wan, Kang-lin
Format Journal Article
LanguageEnglish
Published New Zealand Dove Medical Press Limited 01.01.2021
Taylor & Francis Ltd
Dove
Dove Medical Press
Subjects
Analysis
Antibiotics
Antiparasitic agents
Crystal structure
Crystals
Drug development
Drug resistance
Drug resistance in microorganisms
Genetic aspects
Ligands
Multivariate analysis
Mutation
Mycobacterium tuberculosis
Original Research
Rifampin
rifampin resistance
RNA polymerase
RpoB protein
Statistical analysis
Structure
Tuberculosis
China
North Carolina
United States > US
mutation
rifampin resistance
Mycobacterium tuberculosis
structure
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Summary:To investigate the mutations within the whole gene of and analyze their effects on rifampin (RIF) resistance based on crystal structure. We sequenced the entire gene in 175 tuberculosis isolates and quantified their minimum inhibitory concentrations using microplate-based assays. Additionally, the structural interactions between wild-type/mutant RpoB and RIF were also analyzed. Results revealed that a total of 34 mutations distributed across 17 different sites within the whole gene were identified. Of the 34 mutations, 25 could alter the structural interaction between RpoB and RIF and contribute to RIF resistance. Statistical analysis showed that S450L, H445D, H445Y and H445R mutations were associated with high-level RIF resistance, while D435V was associated with moderate-level RIF resistance. Some mutations within the gene could affect the interaction between RpoB and RIF and thus are associated with RIF resistance. These findings could be helpful to design new antibiotics and develop novel diagnostic tools for drug resistance in TB.
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These authors contributed equally to this work
ISSN:1178-6973
1178-6973
DOI:10.2147/IDR.S333433