rpoB Mutations are Associated with Variable Levels of Rifampin and Rifabutin Resistance in Mycobacterium tuberculosis
Ma-Chao Li,1,* Xiao-Yue Wang,1,* Tong-Yang Xiao,2,* Shi-Qiang Lin,3 Hai-Can Liu,1 Cheng Qian,4 Da Xu,1 Gui-Lian Li,1 Xiu-Qin Zhao,1 Zhi-Guang Liu,1 Li-Li Zhao,1 Kang-Lin Wan1 1State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicab...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-11-01
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| Series: | Infection and Drug Resistance |
| Subjects: | |
| Online Access: | https://www.dovepress.com/rpob-mutations-are-associated-with-variable-levels-of-rifampin-and-rif-peer-reviewed-fulltext-article-IDR |
| _version_ | 1797988086412476416 |
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| author | Li MC Wang XY Xiao TY Lin SQ Liu HC Qian C Xu D Li GL Zhao XQ Liu ZG Zhao LL Wan KL |
| author_facet | Li MC Wang XY Xiao TY Lin SQ Liu HC Qian C Xu D Li GL Zhao XQ Liu ZG Zhao LL Wan KL |
| author_sort | Li MC |
| collection | DOAJ |
| description | Ma-Chao Li,1,* Xiao-Yue Wang,1,* Tong-Yang Xiao,2,* Shi-Qiang Lin,3 Hai-Can Liu,1 Cheng Qian,4 Da Xu,1 Gui-Lian Li,1 Xiu-Qin Zhao,1 Zhi-Guang Liu,1 Li-Li Zhao,1 Kang-Lin Wan1 1State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Bioinformatics, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, People’s Republic of China; 4Beijing Center for Disease Control and Prevention, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Li Zhao; Kang-Lin Wan, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, P.O. Box 5, Changping, Beijing, 102206, People’s Republic of China, Tel/Fax +86 10 58900779, Email zhaolili@icdc.cn; wankanglin@icdc.cnObjective: To assess the relationship between the variant rpoB mutations and the degree of rifampin (RIF)/rifabutin (RFB) resistance in Mycobacterium tuberculosis (M. tuberculosis).Methods: We analyzed the whole rpoB gene in 177 M. tuberculosis clinical isolates and quantified their minimum inhibitory concentrations (MICs) using microplate-based assays.Results: The results revealed that of the 177 isolates, 116 were resistant to both RIF and RFB. There were 38 mutated patterns within the sequenced whole rpoB gene of the 120 isolates. Statistical analysis indicated that mutations, S450L, H445D, H445Y, and H445R, were associated with RIF and RFB resistance. Of these mutations, S450L, H445D, and H445Y were associated with high-level RIF and RFB MIC. H445R was associated with high-level RIF MIC, but not high-level RFB MIC. D435V and L452P were associated with only RIF, but not RFB resistance. Q432K and Q432L were associated with high-level RFB MIC. Several single mutations without statistical association with rifamycin resistance, such as V170F, occurred exclusively in low-level RIF but high-level RFB resistant isolates. Additionally, although cross-resistance to RIF and RFB is common, 21 RIF-resistant/RFB-susceptible isolates were identified.Conclusion: This study highlighted the complexity of rifamycin resistance. Identification of the rpoB polymorphism will be helpful to diagnose the RIF-resistant tuberculosis that has the potential to benefit from a treatment regimen including RFB.Keywords: Mycobacterium tuberculosis, rifampin resistance, rifabutin resistance, mutation |
| first_indexed | 2024-04-11T07:58:37Z |
| format | Article |
| id | doaj.art-c2d64e5d80944b929ab20054390e6494 |
| institution | Directory Open Access Journal |
| issn | 1178-6973 |
| language | English |
| last_indexed | 2024-04-11T07:58:37Z |
| publishDate | 2022-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Infection and Drug Resistance |
| spelling | doaj.art-c2d64e5d80944b929ab20054390e64942022-12-22T04:35:52ZengDove Medical PressInfection and Drug Resistance1178-69732022-11-01Volume 156853686179913rpoB Mutations are Associated with Variable Levels of Rifampin and Rifabutin Resistance in Mycobacterium tuberculosisLi MCWang XYXiao TYLin SQLiu HCQian CXu DLi GLZhao XQLiu ZGZhao LLWan KLMa-Chao Li,1,* Xiao-Yue Wang,1,* Tong-Yang Xiao,2,* Shi-Qiang Lin,3 Hai-Can Liu,1 Cheng Qian,4 Da Xu,1 Gui-Lian Li,1 Xiu-Qin Zhao,1 Zhi-Guang Liu,1 Li-Li Zhao,1 Kang-Lin Wan1 1State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Bioinformatics, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, People’s Republic of China; 4Beijing Center for Disease Control and Prevention, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Li Zhao; Kang-Lin Wan, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, P.O. Box 5, Changping, Beijing, 102206, People’s Republic of China, Tel/Fax +86 10 58900779, Email zhaolili@icdc.cn; wankanglin@icdc.cnObjective: To assess the relationship between the variant rpoB mutations and the degree of rifampin (RIF)/rifabutin (RFB) resistance in Mycobacterium tuberculosis (M. tuberculosis).Methods: We analyzed the whole rpoB gene in 177 M. tuberculosis clinical isolates and quantified their minimum inhibitory concentrations (MICs) using microplate-based assays.Results: The results revealed that of the 177 isolates, 116 were resistant to both RIF and RFB. There were 38 mutated patterns within the sequenced whole rpoB gene of the 120 isolates. Statistical analysis indicated that mutations, S450L, H445D, H445Y, and H445R, were associated with RIF and RFB resistance. Of these mutations, S450L, H445D, and H445Y were associated with high-level RIF and RFB MIC. H445R was associated with high-level RIF MIC, but not high-level RFB MIC. D435V and L452P were associated with only RIF, but not RFB resistance. Q432K and Q432L were associated with high-level RFB MIC. Several single mutations without statistical association with rifamycin resistance, such as V170F, occurred exclusively in low-level RIF but high-level RFB resistant isolates. Additionally, although cross-resistance to RIF and RFB is common, 21 RIF-resistant/RFB-susceptible isolates were identified.Conclusion: This study highlighted the complexity of rifamycin resistance. Identification of the rpoB polymorphism will be helpful to diagnose the RIF-resistant tuberculosis that has the potential to benefit from a treatment regimen including RFB.Keywords: Mycobacterium tuberculosis, rifampin resistance, rifabutin resistance, mutationhttps://www.dovepress.com/rpob-mutations-are-associated-with-variable-levels-of-rifampin-and-rif-peer-reviewed-fulltext-article-IDRmycobacterium tuberculosisrifampin resistancerifabutin resistancemutation |
| spellingShingle | Li MC Wang XY Xiao TY Lin SQ Liu HC Qian C Xu D Li GL Zhao XQ Liu ZG Zhao LL Wan KL rpoB Mutations are Associated with Variable Levels of Rifampin and Rifabutin Resistance in Mycobacterium tuberculosis Infection and Drug Resistance mycobacterium tuberculosis rifampin resistance rifabutin resistance mutation |
| title | rpoB Mutations are Associated with Variable Levels of Rifampin and Rifabutin Resistance in Mycobacterium tuberculosis |
| title_full | rpoB Mutations are Associated with Variable Levels of Rifampin and Rifabutin Resistance in Mycobacterium tuberculosis |
| title_fullStr | rpoB Mutations are Associated with Variable Levels of Rifampin and Rifabutin Resistance in Mycobacterium tuberculosis |
| title_full_unstemmed | rpoB Mutations are Associated with Variable Levels of Rifampin and Rifabutin Resistance in Mycobacterium tuberculosis |
| title_short | rpoB Mutations are Associated with Variable Levels of Rifampin and Rifabutin Resistance in Mycobacterium tuberculosis |
| title_sort | rpob mutations are associated with variable levels of rifampin and rifabutin resistance in mycobacterium tuberculosis |
| topic | mycobacterium tuberculosis rifampin resistance rifabutin resistance mutation |
| url | https://www.dovepress.com/rpob-mutations-are-associated-with-variable-levels-of-rifampin-and-rif-peer-reviewed-fulltext-article-IDR |
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