The Acetate Switch of an Intestinal Pathogen Disrupts Host Insulin Signaling and Lipid Metabolism
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作者:
Hang, Saiyu
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Harvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USAHarvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
Hang, Saiyu
[1
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Purdy, Alexandra E.
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Harvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USAHarvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
Purdy, Alexandra E.
[1
]
Robins, William P.
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Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USAHarvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
Robins, William P.
[2
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Wang, Zhipeng
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Harvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USAHarvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
Wang, Zhipeng
[1
]
Mandal, Manabendra
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Harvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
Tezpur Univ, Dept Mol Biol & Biotechnol, Sonitpur 784028, Assam, IndiaHarvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
Mandal, Manabendra
[1
,3
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Chang, Sarah
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Harvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USAHarvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
Chang, Sarah
[1
]
Mekalanos, John J.
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Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USAHarvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
Mekalanos, John J.
[2
]
Watnick, Paula I.
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Harvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USAHarvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
Watnick, Paula I.
[1
,2
]
机构:
[1] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA
Vibrio cholerae is lethal to the model host Drosophila melanogaster through mechanisms not solely attributable to cholera toxin. To examine additional virulence determinants, we performed a genetic screen in V. cholerae-infected Drosophila and identified the two-component system CrbRS. CrbRS controls transcriptional activation of acetyl-CoA synthase-1 (ACS-1) and thus regulates the acetate switch, in which bacteria transition from excretion to assimilation of environmental acetate. The resultant loss of intestinal acetate leads to deactivation of host insulin signaling and lipid accumulation in enterocytes, resulting in host lethality. These metabolic effects are not observed upon infection with Delta crbS or Delta acs1 V. cholerae mutants. Additionally, uninfected flies lacking intestinal commensals, which supply short chain fatty acids (SCFAs) such as acetate, also exhibit altered insulin signaling and intestinal steatosis, which is reversed upon acetate supplementation. Thus, acetate consumption by V. cholerae alters host metabolism, and dietary acetate supplementation may ameliorate some sequelae of cholera.
机构:
China Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
China Agr Univ, Coll Plant Protect, MOA Key Lab Pest Monitoring & Green Management, Beijing, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Zhu, Lin
Xie, Yuqing
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China Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
China Agr Univ, Coll Plant Protect, MOA Key Lab Pest Monitoring & Green Management, Beijing, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Xie, Yuqing
Liu, Chenxi
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China Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
China Agr Univ, Coll Plant Protect, MOA Key Lab Pest Monitoring & Green Management, Beijing, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Liu, Chenxi
Cheng, Jie
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Shanxi Agr Univ, Dept Entomol Coll Plant Protect, Jinzhong, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Cheng, Jie
Shen, Zhongjian
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Chinese Acad Agr Sci, Inst Plant Protect, State Key Lab Biol Plant Dis & Insect Pests, Key Lab Nat Enemy Insects,Minist Agr & Rural Affai, Beijing, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Shen, Zhongjian
Liu, Xiaoming
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Henan Agr Univ, Coll Plant Protect, State Key Lab Wheat & Maize Crop Sci, Henan Int Lab Green Pest Control, Zhengzhou, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Liu, Xiaoming
Cai, Limei
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China Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
China Agr Univ, Coll Plant Protect, MOA Key Lab Pest Monitoring & Green Management, Beijing, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Cai, Limei
Ning, Xinyuan
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China Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
China Agr Univ, Coll Plant Protect, MOA Key Lab Pest Monitoring & Green Management, Beijing, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Ning, Xinyuan
Zhang, Songdou
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China Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
China Agr Univ, Coll Plant Protect, MOA Key Lab Pest Monitoring & Green Management, Beijing, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Zhang, Songdou
Li, Zhen
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China Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
China Agr Univ, Coll Plant Protect, MOA Key Lab Pest Monitoring & Green Management, Beijing, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Li, Zhen
Huang, Qiuying
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Huazhong Agr Univ, Hubei Insect Resources Utilizat & Sustainable Pest, Wuhan, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
Huang, Qiuying
Liu, Xiaoxia
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China Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
China Agr Univ, Coll Plant Protect, MOA Key Lab Pest Monitoring & Green Management, Beijing, Peoples R ChinaChina Agr Univ, Coll Plant Protect, Dept Entomol, Beijing, Peoples R China
机构:
ARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA
Integr Nutraceut Int, Springhill, TN USAARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA
Qin, Bolin
Dawson, Harry D.
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ARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USAARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA
Dawson, Harry D.
Schoene, Norberta W.
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ARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USAARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA
Schoene, Norberta W.
Polansky, Marilyn M.
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ARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USAARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA
Polansky, Marilyn M.
Anderson, Richard A.
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ARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USAARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA