Genetic Ablation of Butyrate Utilization Attenuates Gastrointestinal Salmonella Disease.
Genetic Ablation of Butyrate Utilization Attenuates Gastrointestinal Salmonella Disease.
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DOI：
10.1016/j.chom.2018.01.004
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发表时间：
2018-02-14
影响因子：
30.3
通讯作者：
Bäumler AJ
中科院分区：
文献类型：
--
作者：
Bronner DN;Faber F;Olsan EE;Byndloss MX;Sayed NA;Xu G;Yoo W;Kim D;Ryu S;Lebrilla CB;Bäumler AJ
伤寒沙门氏菌血清型（S.）伤寒是一种肠外病原体，由引起胃肠道疾病的沙门氏菌血清型演变而来。与非伤寒沙门氏菌血清型相比，伤寒沙门氏菌血清型的基因组包含各种功能丧失突变。然而，这些遗传差异对病原体生态学转变的贡献仍然未知。我们发现，伤寒沙门氏菌中缺失的 ydiQRSTD 操纵子使鼠伤寒沙门氏菌能够在胃肠道疾病期间利用微生物群衍生的丁酸盐。出乎意料的是，丁酸利用的基因消除减少了鼠伤寒沙门氏菌上皮侵袭并减轻了肠道炎症。 ydiD 的缺失使得鼠伤寒沙门氏菌对丁酸盐介导的入侵基因表达抑制敏感。结合毒力相关 (Vi) 荚膜多糖的获得和超长 O 抗原链的丧失（伤寒沙门氏菌的两个特征），丁酸盐利用的基因消除可消除鼠伤寒沙门氏菌引起的肠道炎症。因此，从胃肠道病原体到肠外病原体的转变涉及离散的遗传变化，为病原体的进化和出现提供了见解。布朗纳等人。研究表明，在密切相关的伤寒沙门氏菌基因组中，使伤寒沙门氏菌能够利用微生物群衍生的丁酸盐的基因被删除，从而减轻了病原体引起的肠道炎症。因此，基因丢失有助于病原体从胃肠道向肠外的转变。
Salmonella enterica serovar (S.) Typhi is an extraintestinal pathogen that evolved from Salmonella serovars causing gastrointestinal disease. Compared to non-typhoidal Salmonella serovars, the genomes of typhoidal serovars contain various loss-of-function mutations. However, the contribution of these genetic differences to this shift in pathogen ecology remains unknown. We show that the ydiQRSTD operon, which is deleted in S. Typhi, enables S. Typhimurium to utilize microbiota-derived butyrate during gastrointestinal disease. Unexpectedly, genetic ablation of butyrate utilization reduces S. Typhimurium epithelial invasion and attenuates intestinal inflammation. Deletion of ydiD renders S. Typhimurium sensitive to butyrate-mediated repression of invasion gene expression. Combined with the gain of virulence-associated (Vi) capsular polysaccharide and loss of very-long O antigen chains, two features characteristic of S. Typhi, genetic ablation of butyrate utilization abrogates S. Typhimurium-induced intestinal inflammation. Thus, the transition from a gastrointestinal to extraintestinal pathogen involved discrete genetic changes, providing insights into pathogen evolution and emergence. Bronner et al. show that genes enabling Salmonella enterica serovar (S.) Typhimurium to utilize microbiota-derived butyrate are deleted in the genome of the closely related S. Typhi, thereby moderating intestinal inflammation induced by the pathogen. Thus, gene loss can aid in the transition from gastrointestinal to extraintestinal pathogens.
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影响因子：
30.8
作者：
Holt, Kathryn E.;Parkhill, Julian;Mazzoni, Camila J.;Roumagnac, Philippe;Weill, Francois-Xavier;Goodhead, Ian;Rance, Richard;Baker, Stephen;Maskell, Duncan J.;Wain, John;Dolecek, Christiane;Achtman, Mark;Dougan, Gordon
通讯作者：
Dougan, Gordon
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
5.3
作者：
Campbell, Lioudmila A.;Faivre, Emily J.;Ingraham, Holly A.
通讯作者：
Ingraham, Holly A.
影响因子：
3.1
作者：
Lopez, Christopher A.;Rivera-Chvez, Fabian;Baeumler, Andreas J.
通讯作者：
Baeumler, Andreas J.
影响因子：
3.2
作者：
Martinez, Luary C.;Banda, Maria M.;Bustamante, Victor H.
通讯作者：
Bustamante, Victor H.