title: A novel antimicrobial peptide significantly enhances acid-induced killing of Shiga toxin-producing Escherichia coli O157 and non-O157 serotypes.
abstract: Shiga toxin-producing Escherichia coli (STEC) colonizes the human intestine, causing haemorrhagic colitis and haemolytic uraemic syndrome (HUS). Treatment options are limited to intravenous fluids in part because sublethal doses of some antibiotics have been shown to stimulate increased toxin release and enhance the risk of progression to HUS. Preventative antimicrobial agents, especially those that build on the natural antimicrobial action of the host defence, may provide a better option. In order to survive the acid stress of gastric passage, STEC is equipped with numerous acid resistance and DNA repair mechanisms. Inhibition of acid-induced DNA repair may offer a strategy to target survival of ingested STEC. We report here that brief pretreatment with a novel antimicrobial peptide, which was previously shown to inhibit bacterial DNA repair, significantly and profoundly reduces survival of acid-stressed O157 : H7 and non-O157 : H7 STEC seropathotypes that are highly associated with HUS. Reduction in survival rates of STEC range from 3 to 5 log. We also show that peptide/acid treatment results in little or no increase in toxin production, thereby reducing the risk of progression to HUS. This study identifies the peptide wrwycr as a potential new candidate for a preventative antimicrobial for STEC infection.
authors: Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada.
authors: M
authors: M
authors: Lino
authors: Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada.
authors: J V
authors: JV
authors: Kus
authors: Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada.
authors: S L
authors: SL
authors: Tran
authors: Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada.
authors: Z
authors: Z
authors: Naqvi
authors: Molecular Structure and Function, Hospital for Sick Children, Toronto, ON, Canada.
authors: B
authors: B
authors: Binnington
authors: Division of Biomedical Sciences, Herman Ostrow School of Dentistry of the University of Southern California, USA.
authors: S D
authors: SD
authors: Goodman
authors: Department of Biology, Center for Microbial Sciences and Molecular Biology Institute, San Diego State University, USA.
authors: A M
authors: AM
authors: Segall
authors: Molecular Structure and Function, Hospital for Sick Children, Toronto, ON, Canada.|Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada.
authors: D
authors: D
authors: Barnett Foster
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004926:Escherichia coli / Q000145:classification* / Q000187:drug effects* / Q000502:physiology; D019453:Escherichia coli O157 / Q000187:drug effects* / Q000502:physiology; D006463:Hemolytic-Uremic Syndrome / Q000382:microbiology; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D012703:Serotyping; D022603:Shiga Toxins / Q000096:biosynthesis*; D054323:Shiga-Toxigenic Escherichia coli / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D023181:Antimicrobial Cationic Peptides; D022603:Shiga Toxins; D006851:Hydrochloric Acid