Bacteriophage-based Probiotic Preparation for Managing Shigella Infections

Abstract

During the studies supported by our Phase I STTR grant from the US Army, we began developing and testing a novel concept for a probiotic preparation based on naturally occurring bacteriophages as a way to condition the GI tract s microflora gently and favorably. The preparation (designated ShigActive ) is a bacteriophage cocktail that specifically targets Shigella spp. (significant diarrhea-causing pathogens that sicken ca. 165 million people/year, ca. 1.1 million of whom die). We have successfully isolated and rigorously characterized a large number of phages lytic for Shigella, and we have developed a murine model in which the in vivo efficacy of our phage preparation can be evaluated. During this Phase II project, we propose to perform studies required to obtain regulatory approval of ShigActive and to generate data critical for subsequent clinical trials (performance of actual clinical trials is not stipulated during this Phase II grant). During these studies, we will also perform metagenomic analyses of the gut microbiota (using DGGE and/or state-of-the-art 454-pyrosequencing of 16S rRNA genes) of mice before and after their treatment with ShigActive, in order to (i) obtain additional safety data for the FDA, and (ii) compare rigorously the effect of ShigActive and ampicillin (an antibiotic commonly used to treat shigellosis) on the intestinal microflora of mice.

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Document Details

Document Type
Technical Report
Publication Date
Apr 16, 2015
Accession Number
ADA627266

Entities

People

  • Alexander Sulakvelidze

Tags

DTIC Thesaurus Topics

  • Anti-Bacterial Agents
  • Bacteria
  • Bacteriophages
  • Biological Toxins
  • Birds
  • Blood
  • Blood Cells
  • Caudovirales
  • Cell Count
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Hematologic Tests
  • Leukocytes
  • Medical Personnel
  • Microbiomes
  • Pathogenic Bacteria

Fields of Study

  • Biology

Readers

  • Geochemistry
  • Microbial Pathology
  • Oncology