title: Vibrio vulnificus Secretes an Insulin-degrading Enzyme That Promotes Bacterial Proliferation in Vivo.
abstract: We describe a novel insulin-degrading enzyme, SidC, that contributes to the proliferation of the human bacterial pathogen Vibrio vulnificus in a mouse model. SidC is phylogenetically distinct from other known insulin-degrading enzymes and is expressed and secreted specifically during host infection. Purified SidC causes a significant decrease in serum insulin levels and an increase in blood glucose levels in mice. A comparison of mice infected with wild type V. vulnificus or an isogenic sidC-deletion strain showed that wild type bacteria proliferated to higher levels. Additionally, hyperglycemia leads to increased proliferation of V. vulnificus in diabetic mice. Consistent with these observations, the sid operon was up-regulated in response to low glucose levels through binding of the cAMP-receptor protein (CRP) complex to a region upstream of the operon. We conclude that glucose levels are important for the survival of V. vulnificus in the host, and that this pathogen uses SidC to actively manipulate host endocrine signals, making the host environment more favorable for bacterial survival and growth.
authors.affiliation: From the Department of Life Science, Sogang University, Seoul 121-742, Korea.
authors.forename: In Hwang
authors.initials: IH
authors.lastname: Kim
authors.affiliation: From the Department of Life Science, Sogang University, Seoul 121-742, Korea.
authors.forename: Ik-Jung
authors.initials: IJ
authors.lastname: Kim
authors.affiliation: From the Department of Life Science, Sogang University, Seoul 121-742, Korea.
authors.forename: Yancheng
authors.initials: Y
authors.lastname: Wen
authors.affiliation: From the Department of Life Science, Sogang University, Seoul 121-742, Korea.
authors.forename: Na-Young
authors.initials: NY
authors.lastname: Park
authors.affiliation: the Division of Life Science, Korea University, Seoul 136-701, Korea.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Park
authors.affiliation: From the Department of Life Science, Sogang University, Seoul 121-742, Korea.
authors.forename: Keun-Woo
authors.initials: KW
authors.lastname: Lee
authors.affiliation: From the Department of Life Science, Sogang University, Seoul 121-742, Korea.
authors.forename: Ara
authors.initials: A
authors.lastname: Koh
authors.affiliation: the Division of Life Science, Korea University, Seoul 136-701, Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: the Division of Life Science, Korea University, Seoul 136-701, Korea.
authors.forename: Seung-Hoi
authors.initials: SH
authors.lastname: Koo
authors.affiliation: From the Department of Life Science, Sogang University, Seoul 121-742, Korea, kskim@sogang.ac.kr.
authors.forename: Kun-Soo
authors.initials: KS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood; D007339:Insulysin / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics* / Q000382:microbiology; D014735:Vibrio Infections / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D041261:Vibrio vulnificus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007339:Insulysin
keywords: SidC; Vibrio vulnificus; bacterial pathogenesis; carbohydrate metabolism; host-pathogen interaction; insulin; insulin-degrading enzyme; proteolytic enzyme