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Advances in the development of molecular genetic tools for Mycobacterium tuberculosis

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Journal of Genetics and Genomics 2018年第6期45卷 281-297页

作者： Chiranjibi Chhotaray yaoju tan Julius Mugweru Md Mahmudul Islam H.M.Adnan Hameed Shuai Wang Zhili Lu Changwei Wang Xinjie Li Shouyong tan Jianxiong Liu Tianyu Zhang State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Respiratary Disease Department of Clinical LaboratoryCuangzhou Chest HospitalGuangzhou 510095China Department of Biological Sciences University of EmbuP.O Box 6-60100EmbuKenya

Mycobacterium tuberculosis, a Gram-positive bacterium of great clinical relevance, is a lethal pathogen owing to its complex physiological characteristics and development of drug resistance. Several molecular genetic tools have been developed in the past few decades to study this microorganism. These tools have been instrumental in understanding how M. tuberculosis became a successful pathogen. Advanced molecular genetic tools have played a significant role in exploring the complex pathways involved in M. tuberculosis pathogenesis. Here, we review various molecular genetic tools used in the study of M. tuberculosis. Further, we discuss the applications of clustered regularly interspaced short palindromic repeat interference（CRISPRi）, a novel technology recently applied in M. tuberculosis research to study target gene functions. Finally, prospective outcomes of the applications of molecular techniques in the field of M. tuberculosis genetic research are also discussed.

关键词： Mycobacterium tuberculosis Molecular genetic tools Gram-positive Recombineering Drug resistance

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tNGS在分枝杆菌病诊断中的价值

临床肺科杂志 2024年第9期29卷 1304-1308,1314页

作者：吴睿彦陈品儒邓政先陈慧玉许柳清谭耀驹广州市胸科医院重症结核科内一区/广州市结核病研究重点实验室广东广州510095

目的探讨tNGS检测技术在诊断分枝杆菌病中的应用价值。方法对137例疑诊分枝杆菌病的患者行纤支镜检查,支气管肺泡灌洗液BALF样本送检tNGS检测、分枝杆菌培养+菌种鉴定检查,比较两种检测方法的阳性率。结果通过tNGS检测圣乔治诺卡菌3... 详细信息

目的探讨tNGS检测技术在诊断分枝杆菌病中的应用价值。方法对137例疑诊分枝杆菌病的患者行纤支镜检查,支气管肺泡灌洗液BALF样本送检tNGS检测、分枝杆菌培养+菌种鉴定检查,比较两种检测方法的阳性率。结果通过tNGS检测圣乔治诺卡菌3例。134例分枝杆菌病患者,tNGS对分枝杆菌检测阳性率86.57%,分枝杆菌培养阳性率78.36%,差异没有统计学意义(P>0.05)。对于NTM病检测的tNGS阳性率80.53%,分枝杆菌培养阳性率83.19%;对于活动性结核病,tNGS检测阳性率为100%,分枝杆菌培养阳性率47.6%。tNGS与分枝杆菌培养菌种鉴定应用于分枝杆菌病、NTM病检测报告一致或为同一分枝杆菌复合群仅分别占比58.4%及61.9%,单独应用tNGS对病患做出病原学诊断仍存在假阳性或假阴性可能。结论 tNGS技术逐渐成熟,在临床广泛使用,在鉴定分枝杆菌菌种、鉴别“涂片抗酸染色阳性”的病原体,有较高的参考价值,在确定病原体的诊断时应结合患者病史、临床症状、检查结果等综合分析。

关键词： tNGS 分枝杆菌病非结核分枝杆菌病结核病

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Drug resistance mechanisms and novel drug targets for tuberculosis therapy

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Journal of Genetics and Genomics 2017年第1期44卷 21-37页

作者： Md Mahmudul Islam H.M. Adnan Hameed Julius Mugweru Chiranjibi Chhotaray Changwei Wang yaoju tan Jianxiong Liu Xinjie Li Shouyong tan Iwao Ojima Wing Wai Yew Eric Nuermberger Gyanu Lamichhane Tianyu Zhang State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510530 China University of Chinese Academy of Sciences Beijing 100049 China State Key Laboratory of Respiratory Disease Department of Clinical Laboratory The Guangzhou Chest Hospital Guangzhou 510095 China Institute of Chemical Biology and Drug Discovery Stony Brook University-State University of New York Stony Brook NY 11794-3400 USA Stanley Ho Centre for Emerging Infectious Diseases The Chinese University of Hong Kong Hong Kong Special Administrative Region China Center for Tuberculosis Research Department of Medicine Johns Hopkins University Baltimore MD 21231-1002 USA

Drug-resistant tuberculosis （TB） poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug- resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuber- culosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance.

关键词： Tuberculosis Mycobacterium tuberculosis Resistance Drug target Mechanism

The Influence of Pyrazinamide Monoresistance on Treatment Outcomes in Tuberculosis Patients from Southern China

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Journal of Tuberculosis Research 2016年第1期4卷 9-17页

作者： Shouyong tan Yunwei Rao Jintao Guo yaoju tan Xingshan Cai Haobin Kuang Yanqiong Li Wenyan Liu Julius Mugweru Bangxing Wang Yuanyuan Cao Changwei Wang Ying Zhang Tianyu Zhang State Key Laboratory of Respiratory Disease The Guangzhou Chest Hospital Guangzhou China Respiratory Department Guangzhou Medical University Guangzhou China State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou China W. Harry Feinstone Department of Molecular Microbiology and Immunology Bloomberg School of Public Health Johns Hopkins University Baltimore USA

This study aimed to explore the influence of pyrazinamide (PZA) monoresistance on the treatment outcome of otherwise drug susceptible tuberculosis (TB). A cohort of 194 TB patients that were infected with strains susceptible to isoniazid (INH), rifampin (RIF) and ethambutol (EMB) were included in a retrospective study at the Guangzhou Chest Hospital. We reported 148 (76.3%) PZA- susceptible TB cases and 46 (23.7%) PZA-monoresistance TB cases identified by the BACTEC MGIT 960 system. All patients were treated with the standard 6 months WHO recommended regimen, which included 2 months of INH + RIF + EMB + PZA in the intensive-phase, and the subsequent 4 months of INH + RIF during continuation-phase. Bacterial burden in the lungs was estimated using sputum smear acid-fast bacillary count while the lung lesions and cavitations were examined by X-ray at the end of first 2 months of chemotherapy. After intensive-phase treatment, there were 164 (84.5%) cases of smear-negative conversion and 151 (77.9%) cases of total or partial lesion elimination. The rates of smear-negative conversion (78.3%) and lesion elimination (39.1%) of the PZA-monoresistant patients were similar with the PZA-sensitive group (P > 0.05). However, lung cavitation was more likely to be resolved in PZA-sensitive patients than in the PZA-patients (X2 = 9.623, P = 0.002). The smear-negative conversion rates were 95.9% for the PZA-sensitive patients and 87.0% for the PZA-monoresistant patients after 6 months of treatment (X2 = 3.461, P = 0.063). Together, our data suggest that PZA-monoresistance contributes to the delay of resolution of the lung cavitations in the Southern China population without affecting the sputum conversion and lesion elimination rates.

关键词： Tuberculosis Pyrazinamide Treatment Monoresistance

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《汉语大词典》语词溯源例证指瑕

绍兴文理学院学报（哲学社会科学版） 2001年第2期21卷 56-61页

作者：谭耀炬绍兴文理学院中文系，浙江绍兴312000

是一部权威的大型历史语文词典,在语词溯源及书证等方面比同类辞书都有很大改进.但是,历史语文词典要求语词溯源和例证准确可靠,而对于明代以来产生和使用的词的溯源例证仍有不尽人意之处.本文列举其中一二,以供编撰者修订时参考.

关键词：辞书《汉语大词典》溯原例证词语溯源

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“嬷嬷"考踪

中国典籍与文化 2005年第2期 113-116页

作者：谭耀炬浙江财经学院人文学院

“嬷嬷”是古代戏曲小说常见的称谓,通常用于指称年长妇女。该词《辞源》失收,而《汉语大词典》、《汉语大字典》二书在义项排列、书证的使用上均有不当。本文考证了“嬷嬷”称谓从元代以来数百年间所经历的由泛称到尊称,直至贱称的演变... 详细信息

“嬷嬷”是古代戏曲小说常见的称谓,通常用于指称年长妇女。该词《辞源》失收,而《汉语大词典》、《汉语大字典》二书在义项排列、书证的使用上均有不当。本文考证了“嬷嬷”称谓从元代以来数百年间所经历的由泛称到尊称,直至贱称的演变,并讨论了该称谓从获得亲嫡尊贵义到使用范围下移、亲嫡含义淡化,直至用于称妓院老鸨,称女仆等低贱称谓在文化方面的原因。

关键词：《汉语大词典》《汉语大字典》古代戏曲《辞源》义项排列称谓使用指称书证