Pathogenomics and eco-epidemiology of Mycobacterium orygis, an emerging zoonotic tuberculosis organism

米分枝杆菌（一种新兴的人畜共患结核病微生物）的病理基因组学和生态流行病学

• 批准号: 21K14969
• 负责人: THAPA JEEWAN
• 金额: $ 3万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K14969/
• 关键词: tuberculosis; Mycobacterium orygis; Pathogenomics; molecular epidemiology; Nepal; Tuberculosis; epidemiology

To investigate the pathogenomics of Mycobacterium orygis, an emerging zoonotic tuberculosis (TB) pathogen, we conducted a comparative whole genome analysis of M. orygis isolates that we had obtained. Our findings suggest that M. orygis has developed unique pathogenic strategies that are differ from other members of M. tuberculosis complex. For instance, unlike in M. bovis, there is a different mutation pattern in the anti-Sigk of M. orygis, leading to higher production of mpt70 and mpt83 immunogenic proteins. Furthermore, polymorphisms in gyrB, mmpL6, PPE55, Rv2042c, TbD1 were identified to be M. orygis specific. These genetic characteristics offer the potential for the development of rapid diagnostic methods for the specific detection of M. orygis. We are continuing our in-depth whole genome analysis of our M. orygis isolates by carefully scruntinizing each single nucleotide polymorphisms, insertion and deletion, and genetic recombination to determine their association with M. orygis.We have developed a fecal mycobacterial assay that uses magnetic beads to capture TB DNA, which can later be detected by the LAMP method. When we validated in a field setting in Nepal, we detected TB bacteria in two TB-seropositive elephants. We have isolated four M. tuberculosis isolates from the culture of postmortem TB-suspected lung tissue samples of four captive elephants. We have collaborated for the surveillance of zoonotic TB in Nepal. However, we were unable to detect M. orygis and other zoonotic TB bacteria from human tuberculosis suspected samples in Nepal.

为了研究新出现的人畜共患结核病(TB)病原体--米分枝杆菌的致病基因组学，我们对我们获得的米分枝杆菌分离株进行了比较全基因组分析。我们的发现表明，米色分枝杆菌已经发展出不同于结核分枝杆菌复合体其他成员的独特致病策略。例如，与牛分枝杆菌不同，米分枝杆菌的抗Sigk基因有不同的突变模式，导致mpt70和mpt83免疫原蛋白的产量较高。此外，在gyrB、MMPL6、PPE55、Rv2042c、Tbd1等位基因上的多态性被鉴定为稻瘟病菌所特有的。这些遗传特征为快速诊断方法的发展提供了潜力，可用于特定的米支原体检测。我们正在继续对我们的米氏杆菌分离株进行深入的全基因组分析，仔细分析每个单核苷酸多态、插入和缺失以及基因重组，以确定它们与米氏杆菌的相关性。我们已经开发出一种粪便分枝杆菌检测方法，它使用磁珠来捕获TB DNA，稍后可以用LAMP方法进行检测。当我们在尼泊尔的野外环境中进行验证时，我们在两头结核血清阳性的大象身上检测到了结核病细菌。我们从四头圈养大象死后疑似肺结核的肺组织样本中分离出四株结核分枝杆菌。我们在尼泊尔合作监测人畜共患结核病。然而，我们无法从尼泊尔的疑似人类结核病样本中检测到米氏分枝杆菌和其他人畜共患结核病细菌。

项目成果

Agriculture and Forestry University(ネパール)

农林大学（尼泊尔）

Mycobacterium orygis-associated tuberculosis

米分枝杆菌相关结核病

• 发表时间: 2022
• 作者: Joseph Yamweka Chizimu;Eddie Samuneti Solo;Precious Bwalya;Wimonrat Tanomsridachchai;Herman Chambaro;Misheck Shawa;Thoko Flav Kapalamula;Partick Lungu;Yukari Fukushima;Victor Mukonka;Jeewan Thapa;Chie Nakajima;Yasuhiko Suzuki;Jeewan Thapa
• 通讯作者: Jeewan Thapa

NATA, German Nepal Tuberculosis Project/National Trust for Nature Conservation/Chitwan National Park(ネパール)

NATA、德国尼泊尔结核病项目/国家自然保护信托基金/奇旺国家公园（尼泊尔）

Development of methyl green dry loop-mediated isothermal amplification method for the simple detection of Mycobacterium tuberculosis in clinical samples

甲基绿干环介导等温扩增方法的建立用于简单检测临床样本中的结核分枝杆菌

• 发表时间: 2021
• 作者: Jeewan Thapa;Bhagwan Maharjan;Chie Nakajima;Yasuhiko Suzuki
• 通讯作者: Yasuhiko Suzuki

University Teaching Hospital(ザンビア)

大学教学医院（赞比亚）