Rarity of rpoB Mutations Outside the Rifampicin Resistance-Determining Region of Mycobacterium tuberculosis Isolates from Patients Responding Poorly to First-Line Tuberculosis Regimens in Beijing, China: A Retrospective Study

• Main Authors: Guo J, Liu R, Shi J, Huo F, Shang Y, Wang F, Gao M, Li S
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-07-01
• Series: Infection and Drug Resistance
• Subjects: tuberculosis; rifampicin-resistance; rpob; diagnosis
• Online Access: https://www.dovepress.com/rarity-of-rpob-mutations-outside-the-rifampicin-resistance-determining-peer-reviewed-fulltext-article-IDR

Jidong Guo,1,* Rongmei Liu,1,* Jin Shi,1,* Fengmin Huo,2 Yuanyuan Shang,3 Fen Wang,2 Mengqiu Gao,1 Shanshan Li3 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China; 2National Clinical Laboratory on Tuberculosis, Beijing Key laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China; 3Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shanshan LiDepartment of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of ChinaTel [phone]Fax [phone]Email [e-mail] GaoDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of ChinaTel [phone]Fax [phone]Email [e-mail]: Early and accurate diagnosis of rifampicin (RIF)-resistant Mycobacterium tuberculosis (MTB) is essential for controlling community spread of drug-resistant tuberculosis (TB). In order to discover mutations residing outside the rifampicin resistance-determining region (RRDR) of the MTB rpoB gene, we conducted this retrospective study.Methods: We retrospectively screened patient records to obtain Xpert MTB/RIF assay results for patients who received care at the Beijing Chest Hospital from 2016 to 2019 in order to identify subjects who met study selection criteria. Stored frozen patient isolates were cultured, harvested, and then subjected to drug susceptibility testing. Concurrently, entire rpoB gene DNA of each isolate was amplified and then sequenced to reveal rpoB mutations.Results: Overall, 104 RIF-susceptible tuberculosis patients who were tested using the Xpert MTB/RIF assay also had poor first-line regimen treatment responses. Isolates obtained from these cases included 101 MTB isolates that possessed wild-type rpoB allelic profiles, as demonstrated using Sanger sequencing. However, sequences from the other three isolates confirmed that rpoB of one isolate harbored a mutation encoding the amino acid substitution Ile491Phe and that rpoB genes of two isolates contained a mutation encoding the amino acid substitution Ser450Leu.Conclusion: Our data demonstrated that mutations found outside the RRDR of MTB rpoB are rare in Beijing, China, indicating that World Health Organization-approved molecular diagnostics are generally suitable for diagnosing RIF resistance.Keywords: tuberculosis, rifampicin-resistance, rpoB, diagnosis