The gut commensal Bacteroides thetaiotaomicron exacerbates enteric infection through modification of the metabolic landscape.
The gut commensal Bacteroides thetaiotaomicron exacerbates enteric infection through modification of the metabolic landscape.
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DOI：
10.1016/j.chom.2014.11.005
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发表时间：
2014-12-10
影响因子：
30.3
通讯作者：
Sperandio V
中科院分区：
文献类型：
--
作者：
Curtis MM;Hu Z;Klimko C;Narayanan S;Deberardinis R;Sperandio V
肠道病原体肠出血性大肠杆菌（EHEC）引起严重腹泻，但肠道微生物群对EHEC感染的影响在很大程度上是未知的。多形拟杆菌（Bacteroides thetaiotaomicron，Bt）是微生物群的主要成员，其驻留在EHEC附着位点。我们表明，Bt增强EHEC毒力基因的表达，通过转录因子，Cra，这是功能敏感的糖浓度。这种增强的毒力伴随着EHEC定植所需的附着和消失（AE）病变的形成增加。与微生物菌群耗尽的小鼠相比，在Bt重建的小鼠中感染与EHEC同源的天然小鼠病原体啮齿柠檬酸杆菌导致肠道通透性增加沿着宿主病理学恶化和死亡率。Bt改变了感染部位的代谢物环境，增加了参与细菌异生的代谢物，琥珀酸明显增加，这可以被Cra感知。我们的研究结果表明，微生物群组成影响疾病的结果，并可能解释微生物群组成和疾病易感性之间的联系。
The enteric pathogen enterohemorrhagic Escherichia coli (EHEC) causes severe diarrhea but the influence of the gut microbiota on EHEC infection is largely unknown. A predominant member of the microbiota, Bacteroides thetaiotaomicron (Bt), is resident at EHEC attachment sites. We show that Bt enhances EHEC virulence gene expression through the transcription factor, Cra, which is functionally sensitive to sugar concentrations. This enhanced virulence accompanies increased formation of attaching and effacing (AE) lesions requisite for EHEC colonization. Infection with Citrobacter rodentium, a natural mouse pathogen homologous to EHEC, in Bt-reconstituted mice results in increased gut permeability along with exacerbated host pathology and mortality compared to mice deplete of microflora. Bt modifies the metabolite environment at infection sites, increasing metabolites involved in gluconeogenesis, with stark increases in succinate, which can be sensed by Cra. Our findings suggest that microbiota composition affects disease outcome and may explain links between microbiota composition and disease susceptibility.
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影响因子：
6.7
作者：
Bergstrom KS;Kissoon-Singh V;Gibson DL;Ma C;Montero M;Sham HP;Ryz N;Huang T;Velcich A;Finlay BB;Chadee K;Vallance BA
通讯作者：
Vallance BA
影响因子：
3.2
作者：
CHIN, AM;FELDHEIM, DA;SAIER, MH
通讯作者：
SAIER, MH
影响因子：
30.3
作者：
Gevers D;Kugathasan S;Denson LA;Vázquez-Baeza Y;Van Treuren W;Ren B;Schwager E;Knights D;Song SJ;Yassour M;Morgan XC;Kostic AD;Luo C;González A;McDonald D;Haberman Y;Walters T;Baker S;Rosh J;Stephens M;Heyman M;Markowitz J;Baldassano R;Griffiths A;Sylvester F;Mack D;Kim S;Crandall W;Hyams J;Huttenhower C;Knight R;Xavier RJ
通讯作者：
Xavier RJ
影响因子：
2.2
作者：
De Gregoris, Tristano Bacchetti;Aldred, Nick;Burgess, J. Grant
通讯作者：
Burgess, J. Grant
影响因子：
3.2
作者：
FELDHEIM, DA;CHIN, AM;SAIER, MH
通讯作者：
SAIER, MH