title: Transcription of the plasmid-encoded toxin gene from enteroaggregative Escherichia coli is regulated by a novel co-activation mechanism involving CRP and Fis.
abstract: Enteroaggregative Escherichia coli (EAEC) is a major cause of diarrhoea in developing countries. EAEC 042 is the prototypical strain. EAEC 042 secretes the functionally well-characterized Pet autotransporter toxin that contributes to virulence through its cytotoxic effects on intestinal epithelial cells. Following a global transposon mutagenesis screen of EAEC 042, the transcription factors, CRP and Fis, were identified as essential for transcription of the pet gene. Using both in vivo and in vitro techniques, we show that the pet promoter is co-dependent on CRP and Fis. We present a novel co-activation mechanism whereby CRP is placed at a non-optimal position for transcription initiation, creating dependence on Fis for full activation of pet. This study complements previous findings that establish Fis as a key virulence regulator in EAEC 042.
authors.affiliation: School of Immunity and Infection School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Rossiter
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Browning
authors.forename: Denisse L
authors.initials: DL
authors.lastname: Leyton
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Johnson
authors.forename: Rita E
authors.initials: RE
authors.lastname: Godfrey
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Wardius
authors.forename: Mickael
authors.initials: M
authors.lastname: Desvaux
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Fernando
authors.initials: F
authors.lastname: Ruiz-Perez
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
authors.forename: Stephen J W
authors.initials: SJ
authors.lastname: Busby
authors.forename: Ian R
authors.initials: IR
authors.lastname: Henderson
mesh_terms: D001427:Bacterial Toxins / Q000096:biosynthesis*; D001483:Base Sequence; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism*; D004251:DNA Transposable Elements; D004768:Enterotoxins / Q000096:biosynthesis*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D035021:Factor For Inversion Stimulation Protein / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010957:Plasmids; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D014158:Transcription, Genetic
chemical_list: D001427:Bacterial Toxins; D002373:Cyclic AMP Receptor Protein; D004251:DNA Transposable Elements; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D035021:Factor For Inversion Stimulation Protein; C501034:Fis protein, E coli; C481662:crp protein, E coli; C530786:Pet protein, E coli; D012697:Serine Endopeptidases