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.

为了研究米分枝杆菌（一种新出现的人畜共患结核病（TB）病原体）的病原体组学，我们对获得的米分枝杆菌分离株进行了全基因组比较分析。我们的研究结果表明，米分枝杆菌已经形成了与结核分枝杆菌复合体其他成员不同的独特致病策略。例如，与牛分枝杆菌不同，米分枝杆菌的抗 Sigk 存在不同的突变模式，导致 mpt70 和 mpt83 免疫原性蛋白的产量更高。此外，gyrB、mmpL6、PPE55、Rv2042c、TbD1 的多态性被鉴定为米霉特异性的。这些遗传特征为开发用于特异性检测米霉的快速诊断方法提供了潜力。我们正在继续对我们的米分枝杆菌分离株进行深入的全基因组分析，仔细检查每个单核苷酸多态性、插入和缺失以及基因重组，以确定它们与米分枝杆菌的关联。我们开发了一种粪便分枝杆菌检测方法，该检测使用磁性珠子捕获 TB DNA，随后可通过 LAMP 方法进行检测。当我们在尼泊尔进行实地验证时，我们在两只结核血清阳性大象体内检测到了结核菌。我们从四只圈养大象死后疑似结核病肺组织样本的培养物中分离出四种结核分枝杆菌。我们合作监测尼泊尔的人畜共患结核病。然而，我们无法从尼泊尔的人类结核病疑似样本中检测到米糠菌和其他人畜共患结核菌。

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）

University Teaching Hospital(ザンビア)

大学教学医院（赞比亚）

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