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基于纳米孔的耐药结核病靶向测序(NTS):用于个性化治疗策略和新药开发指导的综合工具。

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

作者信息

Yang Chen, Dai Guangchuan, Guo Yicheng, Wang Tianzhen, Gao Weiwei, Zeng Yi

机构信息

Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing, 211100, China.

Department of Tuberculosis, The Second Hospital of Nanjing, The School of Public Health of Nanjing Medical University, Nanjing, 211166, China.

出版信息

BMC Infect Dis. 2025 Jul 1;25(1):861. doi: 10.1186/s12879-025-11227-4.

DOI:10.1186/s12879-025-11227-4
PMID:40596923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12220424/
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.

摘要

背景

耐多药结核病已成为一个需要立即关注的重大公共卫生问题。核酸等温扩增技术(NTS)是一种创新方法,可直接检测临床样本,无需进行培养。它能够提供关于耐药性更准确、可靠和全面的信息。

方法

我们回顾性收集了2023年12月至2024年12月期间在中国江苏省南京市第二医院结核科就诊的疑似耐多药结核病患者的临床数据。计算了NTS对不同类型耐多药结核病和抗菌药物耐药性的诊断效率。展示了耐药基因、突变氨基酸和突变位点之间的关系。

结果

本研究共纳入107例耐多药结核病患者,其中单耐药结核病43例,多耐药结核病20例,耐多药结核病22例,广泛耐药结核病前期21例,广泛耐药结核病1例。NTS诊断耐多药结核病的准确率在42.9%至93.0%之间。除二线注射药物外,NTS对其他抗结核药物的敏感性超过70%。丝氨酸被确定为rpoB基因(66.2%,49/74)和katG基因(86.3%,44/51)中最常发生突变的氨基酸。此外,embB基因、rpsL基因和gyrA基因中最常发生突变的氨基酸分别为蛋氨酸(94.7%,44/51)、赖氨酸(100%,28/28)和天冬氨酸(66.7%,20/30)。

结论

NTS能够有效且精确地提供全面的耐药结果,协助医疗专业人员制定更个性化的治疗方案。此外,它将促进新型抗结核药物的研发,拓宽耐多药结核病的临床治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7545/12220424/a177acc33a8f/12879_2025_11227_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7545/12220424/98d247a88efe/12879_2025_11227_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7545/12220424/d92c03639e77/12879_2025_11227_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7545/12220424/fbdf72169117/12879_2025_11227_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7545/12220424/a177acc33a8f/12879_2025_11227_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7545/12220424/98d247a88efe/12879_2025_11227_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7545/12220424/d92c03639e77/12879_2025_11227_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7545/12220424/fbdf72169117/12879_2025_11227_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7545/12220424/a177acc33a8f/12879_2025_11227_Fig4_HTML.jpg

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