RpoB mutations and effects on rifampin resistance in mycobacterium tuberculosis

Li，Ma Chao1; Lu，Jie2; Lu，Yao1,3; Xiao，Tong Yang4; Liu，Hai Can1; Lin，Shi Qiang5; Xu，Da1; Li，Gui Lian1; Zhao，Xiu Qin1; Liu，Zhi Guang1; Zhao，Li Li1; Wan，Kang Lin1

2021

10.2147/IDR.S333433

Infection and Drug Resistance   影响因子和分区

1178-6973

Objective: To investigate the mutations within the whole rpoB gene of Mycobacterium tuberculosis and analyze their effects on rifampin (RIF) resistance based on crystal structure. Methods: We sequenced the entire rpoB 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: Results revealed that a total of 34 mutations distributed across 17 different sites within the whole rpoB 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. Conclusion: Some mutations within the rpoB 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.

Mutation Mycobacterium tuberculosis Rifampin resistance Structure

SCI

英语

其他

WOS:000707363400005

2-s2.0-85117243915

Scopus

1.State Key Laboratory of Infectious Disease Prevention and Control,National Institute for Communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing,China
2.Beijing Key Laboratory for Pediatric Diseases of Otolaryngology,Head and Neck Surgery,MOE Key Laboratory of Major Diseases in Children,Beijing Pediatric Research Institute,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing,China
3.School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou,China
4.Guangdong Key Laboratory for Diagnosis & Treatment of Emerging Infectious Diseases,Shenzhen Third People’s Hospital,Southern University of Science and Technology,Shenzhen,China
5.Department of Bioinformatics,College of Life Sciences,Fujian Agriculture and Forestry University,Fuzhou,China

Li，Ma Chao,Lu，Jie,Lu，Yao,et al. RpoB mutations and effects on rifampin resistance in mycobacterium tuberculosis[J]. Infection and Drug Resistance,2021,14:4119-4128.

Li，Ma Chao.,Lu，Jie.,Lu，Yao.,Xiao，Tong Yang.,Liu，Hai Can.,...&Wan，Kang Lin.(2021).RpoB mutations and effects on rifampin resistance in mycobacterium tuberculosis.Infection and Drug Resistance,14,4119-4128.

Li，Ma Chao,et al."RpoB mutations and effects on rifampin resistance in mycobacterium tuberculosis".Infection and Drug Resistance 14(2021):4119-4128.