Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features.
Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features.
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对多药耐药性结核分枝杆菌克隆爆发北京菌株对宿主细胞环境的转录反应揭示了其致病特征。
DOI：
10.1038/s41598-021-82905-x
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发表时间：
2021-02-04
影响因子：
4.6
通讯作者：
Ponpuak M
中科院分区：
文献类型：
--
作者：
Aiewsakun P;Prombutara P;Siregar TAP;Laopanupong T;Kanjanasirirat P;Khumpanied T;Borwornpinyo S;Tong-Ngam P;Tubsuwan A;Srilohasin P;Chaiprasert A;Ruangchai W;Palittapongarnpim P;Prammananan T;VanderVen BC;Ponpuak M
结核病是一个全球性的公共卫生问题，出现了多药耐药感染。以前在泰国进行的结核病流行病学研究已经确定了坎恰纳布里的结核分枝杆菌多药耐药菌株的克隆爆发，称为“MKR超级传播者”，后来发现这种特定菌株也传播到其他地区。在这项研究中，我们通过RNA-Seq分析阐明了它的生物学，并确定了一组参与胆固醇降解的基因，这些基因在巨噬细胞感染期间在MKR中上调，但在H37 Rv参考菌株中没有上调。我们还发现，细菌在其细胞内生长阶段上调与ESX-1分泌系统相关的基因，而H37 Rv没有。所有结果均通过qRT-PCR确认。此外，我们发现，以前显示抑制分枝杆菌ESX-1分泌系统和胆固醇利用的化合物，以及FDA批准的已知干扰宿主胆固醇转运的药物，与未处理的对照相比，能够降低MKR的细胞内存活，而不是H37 Rv。总之，我们的研究结果表明，这些途径对MKR的细胞内生长很重要，并且可能成为发现针对这种新兴的多药耐药M菌株的新药的靶点。结核
Tuberculosis is a global public health problem with emergence of multidrug-resistant infections. Previous epidemiological studies of tuberculosis in Thailand have identified a clonal outbreak multidrug-resistant strain of Mycobacterium tuberculosis in the Kanchanaburi province, designated “MKR superspreader”, and this particular strain later was found to also spread to other regions. In this study, we elucidated its biology through RNA-Seq analyses and identified a set of genes involved in cholesterol degradation to be up-regulated in the MKR during the macrophage cell infection, but not in the H37Rv reference strain. We also found that the bacterium up-regulated genes associated with the ESX-1 secretion system during its intracellular growth phase, while the H37Rv did not. All results were confirmed by qRT-PCR. Moreover, we showed that compounds previously shown to inhibit the mycobacterial ESX-1 secretion system and cholesterol utilisation, and FDA-approved drugs known to interfere with the host cholesterol transportation were able to decrease the intracellular survival of the MKR when compared to the untreated control, while not that of the H37Rv. Altogether, our findings suggested that such pathways are important for the MKR’s intracellular growth, and potentially could be targets for the discovery of new drugs against this emerging multidrug-resistant strain of M. tuberculosis.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4.4
作者：
Gideon, Hannah P.;Flynn, JoAnne L.
通讯作者：
Flynn, JoAnne L.
影响因子：
3.6
作者：
Chen, Jeffrey M.;Zhang, Ming;Cole, Stewart T.
通讯作者：
Cole, Stewart T.
影响因子：
4.8
作者：
Dresen, Carola;Lin, Leo Y. -C.;Eltis, Lindsay D.
通讯作者：
Eltis, Lindsay D.
结核分枝杆菌复杂的遗传多样性：挖掘第四个国际螺旋型数据库（SpoldB4），用于分类，种群遗传学和流行病学。
影响因子：
4.2
作者：
Brudey K;Driscoll JR;Rigouts L;Prodinger WM;Gori A;Al-Hajoj SA;Allix C;Aristimuño L;Arora J;Baumanis V;Binder L;Cafrune P;Cataldi A;Cheong S;Diel R;Ellermeier C;Evans JT;Fauville-Dufaux M;Ferdinand S;Garcia de Viedma D;Garzelli C;Gazzola L;Gomes HM;Guttierez MC;Hawkey PM;van Helden PD;Kadival GV;Kreiswirth BN;Kremer K;Kubin M;Kulkarni SP;Liens B;Lillebaek T;Ho ML;Martin C;Martin C;Mokrousov I;Narvskaïa O;Ngeow YF;Naumann L;Niemann S;Parwati I;Rahim Z;Rasolofo-Razanamparany V;Rasolonavalona T;Rossetti ML;Rüsch-Gerdes S;Sajduda A;Samper S;Shemyakin IG;Singh UB;Somoskovi A;Skuce RA;van Soolingen D;Streicher EM;Suffys PN;Tortoli E;Tracevska T;Vincent V;Victor TC;Warren RM;Yap SF;Zaman K;Portaels F;Rastogi N;Sola C
通讯作者：
Sola C