title: Adhesin degradation accelerates delivery of heat-labile toxin by enterotoxigenic Escherichia coli.
abstract: Many enteric pathogens, including enterotoxigenic Escherichia coli (ETEC), produce one or more serine proteases that are secreted via the autotransporter (or type V) bacterial secretion pathway. These molecules have collectively been referred to as SPATE proteins (serine protease autotransporter of the Enterobacteriaceae). EatA, an autotransporter previously identified in ETEC, possesses a functional serine protease motif within its secreted amino-terminal passenger domain. Although this protein is expressed by many ETEC strains and is highly immunogenic, its precise function is unknown. Here, we demonstrate that EatA degrades a recently characterized adhesin, EtpA, resulting in modulation of bacterial adhesion and accelerated delivery of the heat-labile toxin, a principal ETEC virulence determinant. Antibodies raised against the passenger domain of EatA impair ETEC delivery of labile toxin to epithelial cells suggesting that EatA may be an effective target for vaccine development.
authors.affiliation: Department of Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee 38163, USA.
authors.forename: Koushik
authors.initials: K
authors.lastname: Roy
authors.forename: Rita
authors.initials: R
authors.lastname: Kansal
authors.forename: Scott R
authors.initials: SR
authors.lastname: Bartels
authors.forename: David J
authors.initials: DJ
authors.lastname: Hamilton
authors.forename: Salwa
authors.initials: S
authors.lastname: Shaaban
authors.forename: James M
authors.initials: JM
authors.lastname: Fleckenstein
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D058947:Bacterial Secretion Systems / Q000502:physiology*; D001427:Bacterial Toxins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D054307:Enterotoxigenic Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D004768:Enterotoxins / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D022361:Escherichia coli Vaccines / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010447:Peptide Hydrolases; D021381:Protein Transport / Q000502:physiology
chemical_list: D058947:Bacterial Secretion Systems; D001427:Bacterial Toxins; D002352:Carrier Proteins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; C027538:heat-labile enterotoxin, E coli; C483578:EatA protein, E coli; D010447:Peptide Hydrolases