title: Bacteriophage administration significantly reducesShigellacolonization and shedding byShigella-challenged mice without deleterious side effects and distortions in the gut microbiota.
abstract: We used a mouse model to establish safety and efficacy of a bacteriophage cocktail, ShigActive™, in reducing fecalShigellacounts after oral challenge with a susceptible strain. Groups of inbred C57BL/6J mice challenged withShigella sonneistrain S43-NalAcR were treated with a phage cocktail (ShigActive™) composed of 5 lyticShigellabacteriophages and ampicillin. The treatments were administered (i) 1 h after, (ii) 3 h after, (iii) 1 h before and after, and (iv) 1 h before bacterial challenge. The treatment regimens elicited a 10- to 100-fold reduction in the CFU's of the challenge strain in fecal and cecum specimens compared to untreated control mice, (P < 0.05). ShigActiveTMtreatment was at least as effective as treatment with ampicillin but had a significantly less impact on the gut microbiota. Long-term safety studies did not identify any side effects or distortions in overall gut microbiota associated with bacteriophage administration.Shigellaphages may be therapeutically effective in a "classical phage therapy" approach, at least during the early stages afterShigellaingestion. Oral prophylactic "phagebiotic" administration of lytic bacteriophages may help to maintain a healthy gut microbiota by killing specifically targeted bacterial pathogens in the GI tract, without deleterious side effects and without altering the normal gut microbiota.
authors.affiliation: Department of Epidemiology and Emerging Pathogens Institute; University of Florida ; Gainesville, FL USA.
authors.forename: Volker
authors.initials: V
authors.lastname: Mai
authors.affiliation: Department of Epidemiology and Emerging Pathogens Institute; University of Florida ; Gainesville, FL USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Ukhanova
authors.affiliation: Department of Pathology; University of Florida ; Gainesville, FL USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Reinhard
authors.affiliation: Intralytix, Inc. ; Baltimore, MD USA.
authors.forename: Manrong
authors.initials: M
authors.lastname: Li
authors.affiliation: Intralytix, Inc. ; Baltimore, MD USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sulakvelidze
keywords: Shigella; bacteriophage; diarrhea; phage; phagebiotics; probiotics; shigellosis