Nanopore-based targeted sequencing (NTS) for drug-resistant tuberculosis: an integrated tool for personalized treatment strategies and guidance for new drug development

Abstract Background Drug-resistant tuberculosis has emerged as a major public health issue that requires immediate attention. NTS is an innovative method that allows for the direct detection of clinical samples without the need for culture. It could provide more accurate, reliable, and comprehensive...

Full description

Saved in:
Bibliographic Details
Main Authors: Chen Yang, Guangchuan Dai, Yicheng Guo, Tianzhen Wang, Weiwei Gao, Yi Zeng
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Infectious Diseases
Subjects:
Online Access:https://doi.org/10.1186/s12879-025-11227-4
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849769512926183424
author Chen Yang
Guangchuan Dai
Yicheng Guo
Tianzhen Wang
Weiwei Gao
Yi Zeng
author_facet Chen Yang
Guangchuan Dai
Yicheng Guo
Tianzhen Wang
Weiwei Gao
Yi Zeng
author_sort Chen Yang
collection DOAJ
description Abstract Background Drug-resistant tuberculosis has emerged as a major public health issue that requires immediate attention. NTS is an innovative method that allows for the direct detection of clinical samples without the need for culture. It could provide more accurate, reliable, and comprehensive information on drug resistance. Methods We collected clinical data retrospectively from patients suspected of having drug-resistant tuberculosis who visited the tuberculosis department at the Second Hospital of Nanjing in Jiangsu Province, China, from December 2023 to December 2024. The diagnostic efficiency of NTS for different types of drug-resistant tuberculosis and antimicrobial resistance was calculated. The relationship between resistance genes, mutated amino acids, and mutation sites was demonstrated. Results In this study, a total of 107 patients with drug-resistant tuberculosis were included, comprising 43 cases of mono-drug resistant tuberculosis, 20 patients with poly-drug resistant tuberculosis, 22 cases of multidrug-resistant tuberculosis, 21 cases of pre-extensively drug-resistant tuberculosis and 1 case of extensively drug-resistant tuberculosis. The accuracy of NTS in diagnosing drug-resistant tuberculosis ranged from 42.9 to 93.0%. Except for second-line injectable drugs, NTS achieved a sensitivity of over 70% for other anti-tuberculosis drugs. Serine was identified as the most frequently mutated amino acid in both the rpoB gene (66.2%, 49/74) and the katG gene (86.3%, 44/51). Additionally, the most frequently mutated amino acids in the embB gene, rpsL gene, and gyrA gene were methionine (94.7%, 44/51), lysine (100%, 28/28), and aspartic acid (66.7%, 20/30), respectively. Conclusion NTS could effectively and precisely deliver comprehensive drug resistance results, assisting medical professionals to create more personalized treatment plans. Besides, it would encourage the development of new anti-tuberculosis drugs to broaden clinical treatment options for drug-resistant tuberculosis.
format Article
id doaj-art-67a31b8de7d44fbb9a965ebe8d0b9e96
institution DOAJ
issn 1471-2334
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series BMC Infectious Diseases
spelling doaj-art-67a31b8de7d44fbb9a965ebe8d0b9e962025-08-20T03:03:24ZengBMCBMC Infectious Diseases1471-23342025-07-0125111410.1186/s12879-025-11227-4Nanopore-based targeted sequencing (NTS) for drug-resistant tuberculosis: an integrated tool for personalized treatment strategies and guidance for new drug developmentChen Yang0Guangchuan Dai1Yicheng Guo2Tianzhen Wang3Weiwei Gao4Yi Zeng5Department of Tuberculosis, The Second Hospital of NanjingDepartment of Tuberculosis, The Second Hospital of NanjingDepartment of Tuberculosis, The Second Hospital of Nanjing, The School of Public Health of Nanjing Medical UniversityDepartment of Tuberculosis, The Second Hospital of NanjingDepartment of Tuberculosis, The Second Hospital of NanjingDepartment of Tuberculosis, The Second Hospital of NanjingAbstract Background Drug-resistant tuberculosis has emerged as a major public health issue that requires immediate attention. NTS is an innovative method that allows for the direct detection of clinical samples without the need for culture. It could provide more accurate, reliable, and comprehensive information on drug resistance. Methods We collected clinical data retrospectively from patients suspected of having drug-resistant tuberculosis who visited the tuberculosis department at the Second Hospital of Nanjing in Jiangsu Province, China, from December 2023 to December 2024. The diagnostic efficiency of NTS for different types of drug-resistant tuberculosis and antimicrobial resistance was calculated. The relationship between resistance genes, mutated amino acids, and mutation sites was demonstrated. Results In this study, a total of 107 patients with drug-resistant tuberculosis were included, comprising 43 cases of mono-drug resistant tuberculosis, 20 patients with poly-drug resistant tuberculosis, 22 cases of multidrug-resistant tuberculosis, 21 cases of pre-extensively drug-resistant tuberculosis and 1 case of extensively drug-resistant tuberculosis. The accuracy of NTS in diagnosing drug-resistant tuberculosis ranged from 42.9 to 93.0%. Except for second-line injectable drugs, NTS achieved a sensitivity of over 70% for other anti-tuberculosis drugs. Serine was identified as the most frequently mutated amino acid in both the rpoB gene (66.2%, 49/74) and the katG gene (86.3%, 44/51). Additionally, the most frequently mutated amino acids in the embB gene, rpsL gene, and gyrA gene were methionine (94.7%, 44/51), lysine (100%, 28/28), and aspartic acid (66.7%, 20/30), respectively. Conclusion NTS could effectively and precisely deliver comprehensive drug resistance results, assisting medical professionals to create more personalized treatment plans. Besides, it would encourage the development of new anti-tuberculosis drugs to broaden clinical treatment options for drug-resistant tuberculosis.https://doi.org/10.1186/s12879-025-11227-4Drug-resistant tuberculosis(DR-TB)Drug-resistant genesNanopore-based targeted sequencing(NTS)Targeted next-generation sequencing(tNGS)Amino acids
spellingShingle Chen Yang
Guangchuan Dai
Yicheng Guo
Tianzhen Wang
Weiwei Gao
Yi Zeng
Nanopore-based targeted sequencing (NTS) for drug-resistant tuberculosis: an integrated tool for personalized treatment strategies and guidance for new drug development
BMC Infectious Diseases
Drug-resistant tuberculosis(DR-TB)
Drug-resistant genes
Nanopore-based targeted sequencing(NTS)
Targeted next-generation sequencing(tNGS)
Amino acids
title Nanopore-based targeted sequencing (NTS) for drug-resistant tuberculosis: an integrated tool for personalized treatment strategies and guidance for new drug development
title_full Nanopore-based targeted sequencing (NTS) for drug-resistant tuberculosis: an integrated tool for personalized treatment strategies and guidance for new drug development
title_fullStr Nanopore-based targeted sequencing (NTS) for drug-resistant tuberculosis: an integrated tool for personalized treatment strategies and guidance for new drug development
title_full_unstemmed Nanopore-based targeted sequencing (NTS) for drug-resistant tuberculosis: an integrated tool for personalized treatment strategies and guidance for new drug development
title_short Nanopore-based targeted sequencing (NTS) for drug-resistant tuberculosis: an integrated tool for personalized treatment strategies and guidance for new drug development
title_sort nanopore based targeted sequencing nts for drug resistant tuberculosis an integrated tool for personalized treatment strategies and guidance for new drug development
topic Drug-resistant tuberculosis(DR-TB)
Drug-resistant genes
Nanopore-based targeted sequencing(NTS)
Targeted next-generation sequencing(tNGS)
Amino acids
url https://doi.org/10.1186/s12879-025-11227-4
work_keys_str_mv AT chenyang nanoporebasedtargetedsequencingntsfordrugresistanttuberculosisanintegratedtoolforpersonalizedtreatmentstrategiesandguidancefornewdrugdevelopment
AT guangchuandai nanoporebasedtargetedsequencingntsfordrugresistanttuberculosisanintegratedtoolforpersonalizedtreatmentstrategiesandguidancefornewdrugdevelopment
AT yichengguo nanoporebasedtargetedsequencingntsfordrugresistanttuberculosisanintegratedtoolforpersonalizedtreatmentstrategiesandguidancefornewdrugdevelopment
AT tianzhenwang nanoporebasedtargetedsequencingntsfordrugresistanttuberculosisanintegratedtoolforpersonalizedtreatmentstrategiesandguidancefornewdrugdevelopment
AT weiweigao nanoporebasedtargetedsequencingntsfordrugresistanttuberculosisanintegratedtoolforpersonalizedtreatmentstrategiesandguidancefornewdrugdevelopment
AT yizeng nanoporebasedtargetedsequencingntsfordrugresistanttuberculosisanintegratedtoolforpersonalizedtreatmentstrategiesandguidancefornewdrugdevelopment