The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7.
Classical studies have focused on the role that individual regulators play in controlling virulence gene expression. An emerging theme, however, is that bacterial metabolism also plays a key role in this process. Our previous work identified a series of proteins that were implicated in the regulation of virulence. One of these proteins was AdhE, a bi-functional acetaldehyde-CoA dehydrogenase and alcohol dehydrogenase. Deletion of its gene (adhE) resulted in elevated levels of extracellular acetate and a stark pleiotropic phenotype: strong suppression of the Type Three Secretion System (T3SS) and overexpression of non-functional flagella. Correspondingly, the adhE mutant bound poorly to host cells and was unable to swim. Furthermore, the mutant was significantly less virulent than its parent when tested in vivo, which supports the hypothesis that attachment and motility are central to the colonization process. The molecular basis by which AdhE affects virulence gene regulation was found to be multifactorial, involving acetate-stimulated transcription of flagella expression and post-transcriptional regulation of the T3SS through Hfq. Our study reveals fascinating insights into the links between bacterial physiology, the expression of virulence genes, and the underlying molecular mechanism mechanisms by which these processes are regulated.
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Katherine S H
KS
Beckham
James P R
JP
Connolly
Jennifer M
JM
Ritchie
Dai
D
Wang
Jayde A
JA
Gawthorne
Amin
A
Tahoun
David L
DL
Gally
Karl
K
Burgess
Richard J
RJ
Burchmore
Brian O
BO
Smith
Scott A
SA
Beatson
Olwyn
O
Byron
Alan J
AJ
Wolfe
Gillian R
GR
Douce
Andrew J
AJ
Roe
D000085:Acetates / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000382:microbiology* / Q000473:pathology; D019453:Escherichia coli O157 / Q000201:enzymology / Q000472:pathogenicity* / Q000502:physiology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005407:Flagella / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D035001:Host Factor 1 Protein / Q000378:metabolism*; D011817:Rabbits; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D000085:Acetates; D029968:Escherichia coli Proteins; C087373:Hfq protein, E coli; D035001:Host Factor 1 Protein; D037521:Virulence Factors; D000426:Alcohol Dehydrogenase; C068383:adhE protein, E coli; D000445:Aldehyde Oxidoreductases