title: An Escherichia coli O157-specific engineered pyocin prevents and ameliorates infection by E. coli O157:H7 in an animal model of diarrheal disease.
abstract: AvR2-V10.3 is an engineered R-type pyocin that specifically kills Escherichia coli O157, an enteric pathogen that is a major cause of food-borne diarrheal disease. New therapeutics to counteract E. coli O157 are needed, as currently available antibiotics can exacerbate the consequences of infection. We show here that orogastric administration of AvR2-V10.3 can prevent or ameliorate E. coli O157:H7-induced diarrhea and intestinal inflammation in an infant rabbit model of infection when the compound is administered either in a postexposure prophylactic regimen or after the onset of symptoms. Notably, administration of AvR2-V10.3 also reduces bacterial carriage and fecal shedding of this pathogen. Our findings support the further development of pathogen-specific R-type pyocins as a way to treat enteric infections.
authors.affiliation: Channing Laboratory, Brigham and Women’s Hospital/Harvard Medical School and HHMI, 181 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Ritchie
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Greenwich
authors.forename: Brigid M
authors.initials: BM
authors.lastname: Davis
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Dana
authors.initials: D
authors.lastname: Gebhart
authors.forename: Steven R
authors.initials: SR
authors.lastname: Williams
authors.forename: David
authors.initials: D
authors.lastname: Martin
authors.forename: Dean
authors.initials: D
authors.lastname: Scholl
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Waldor
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D058491:Bacterial Load / Q000187:drug effects; D003967:Diarrhea / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control; D019453:Escherichia coli O157 / Q000187:drug effects* / Q000472:pathogenicity; D005243:Feces / Q000382:microbiology; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D011709:Pyocins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D011709:Pyocins