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
]
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
]
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
]
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:
ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA
Integr Nutraceut Int, Springhill, TN USAARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA
Qin, Bolin
Polansky, Marilyn M.
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ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USAARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA
Polansky, Marilyn M.
Dawson, Harry
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ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USAARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA
Dawson, Harry
Anderson, Richard A.
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ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USAARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA
机构:
Tulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
Tulane Univ, Sch Med, Dept Struct & Cellular Biol, New Orleans, LA 70112 USA
Tulane Canc Ctr, New Orleans, LA USA
Louisiana Canc Res Consortium, New Orleans, LA USATulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
Blask, David E.
Dauchy, Robert T.
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Tulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
Tulane Univ, Sch Med, Dept Struct & Cellular Biol, New Orleans, LA 70112 USA
Tulane Canc Ctr, New Orleans, LA USA
Louisiana Canc Res Consortium, New Orleans, LA USATulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
Dauchy, Robert T.
Dauchy, Erin M.
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Tulane Univ, Sch Med, Dept Struct & Cellular Biol, New Orleans, LA 70112 USA
Tulane Canc Ctr, New Orleans, LA USA
Louisiana Canc Res Consortium, New Orleans, LA USATulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
Dauchy, Erin M.
Mao, Lulu
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Tulane Univ, Sch Med, Dept Struct & Cellular Biol, New Orleans, LA 70112 USA
Tulane Canc Ctr, New Orleans, LA USA
Louisiana Canc Res Consortium, New Orleans, LA USATulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
Mao, Lulu
Hill, Steven M.
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Tulane Univ, Sch Med, Dept Struct & Cellular Biol, New Orleans, LA 70112 USA
Tulane Canc Ctr, New Orleans, LA USA
Louisiana Canc Res Consortium, New Orleans, LA USATulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
Hill, Steven M.
Greene, Michael W.
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Mary Imogene Bassett Hosp, Bassett Res Inst, Cooperstown, NY 13326 USATulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
Greene, Michael W.
Belancio, Victoria P.
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Tulane Univ, Sch Med, Dept Struct & Cellular Biol, New Orleans, LA 70112 USA
Tulane Canc Ctr, New Orleans, LA USA
Louisiana Canc Res Consortium, New Orleans, LA USATulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
Belancio, Victoria P.
Sauer, Leonard A.
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Tulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USATulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
Sauer, Leonard A.
Davidson, Leslie
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Mary Imogene Bassett Hosp, Bassett Res Inst, Cooperstown, NY 13326 USATulane Univ, Sch Med, Lab Chrononeuroendocrine Oncol, New Orleans, LA 70112 USA
机构:
Univ Chinese Acad Sci, Med Sch, Beijing 101400, Peoples R China
Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing Key Lab New Drug Mech & Pharmacol Evaluat, Beijing 100050, Peoples R ChinaUniv Chinese Acad Sci, Med Sch, Beijing 101400, Peoples R China
Zhang, Xiao-lin
Wang, Ya-nan
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Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing Key Lab New Drug Mech & Pharmacol Evaluat, Beijing 100050, Peoples R ChinaUniv Chinese Acad Sci, Med Sch, Beijing 101400, Peoples R China
Wang, Ya-nan
Ma, Lu-yao
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Univ Chinese Acad Sci, Med Sch, Beijing 101400, Peoples R ChinaUniv Chinese Acad Sci, Med Sch, Beijing 101400, Peoples R China
Ma, Lu-yao
Liu, Zhong-sheng
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Univ Chinese Acad Sci, Med Sch, Beijing 101400, Peoples R ChinaUniv Chinese Acad Sci, Med Sch, Beijing 101400, Peoples R China
Liu, Zhong-sheng
Ye, Fei
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Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing Key Lab New Drug Mech & Pharmacol Evaluat, Beijing 100050, Peoples R ChinaUniv Chinese Acad Sci, Med Sch, Beijing 101400, Peoples R China
Ye, Fei
Yang, Jian-hong
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Univ Chinese Acad Sci, Med Sch, Beijing 101400, Peoples R ChinaUniv Chinese Acad Sci, Med Sch, Beijing 101400, Peoples R China