A Bacteriophage Cocktail Significantly Reduces Listeria monocytogenes without Deleterious Impact on the Commensal Gut Microbiota under Simulated Gastrointestinal Conditions.

Rasmus Riemer Jakobsen,Louise Bomholtz,Dennis Sandris Nielsen,Signe Kristine Brok-Lauridsen,Alexander Sulakvelidze,Jimmy T Trinh

doi:10.3390/v14020190

Rasmus Riemer Jakobsen, Louise Bomholtz + Show 4 more

Open Access

https://doi.org/10.3390/v14020190

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Journal: Viruses	Publication Date: Jan 19, 2022
Citations: 14	License type: CC BY 4.0

Affiliation: University of Copenhagen, Intralytix (United States)

Abstract

In this study, we examined the effect of a bacteriophage cocktail (tentatively designated as the Foodborne Outbreak Pill (FOP)) on the levels of Listeria monocytogenes in simulated small intestine, large intestine, and Caco-2 model systems. We found that FOP survival during simulated passage of the upper gastrointestinal was dependent on stomach pH, and that FOP robustly inhibited L. monocytogenes levels with effectiveness comparable to antibiotic treatment (ampicillin) under simulated ilium and colon conditions. The FOP did not inhibit the commensal bacteria, whereas ampicillin treatment led to dysbiosis-like conditions. The FOP was also more effective than an antibiotic in protecting Caco-2 cells from adhesion and invasion by L. monocytogenes (5-log reduction vs. 1-log reduction) while not triggering an inflammatory response. Our data suggested that the FOP may provide a robust protection against L. monocytogenes should the bacterium enter the human gastrointestinal tract (e.g., by consumption of contaminated food), without deleterious impact on the commensal bacteria.

Highlights

Listeria monocytogenes is a facultative anaerobic Gram-positive bacterium responsible for many cases of foodborne illness, manifesting as gastroenteritis, meningitis, encephalitis, mother-to-fetus infections, and septicemia
The Foodborne Outbreak Pill (FOP) bacteriophage cocktail was created by Intralytix Inc. by combining, in approximately equal concentrations, three Food and Drug Administration (FDA)-cleared commercial phage preparations currently marketed in the United States for food-safety applications: ListShieldTM, EcoShield PXTM
The Smallest Intestine (TSI) model was used to investigate the ability of the bacteriophage cocktail to endure digestive tract conditions and reduce L. monocytogenes levels in the ileum

Summary

Introduction

Listeria monocytogenes is a facultative anaerobic Gram-positive bacterium responsible for many cases of foodborne illness, manifesting as gastroenteritis, meningitis, encephalitis, mother-to-fetus infections, and septicemia. The diverse clinical manifestations of L. monocytogenes are a result of its ability to enter both macrophages and other cell types, where it can survive and multiply [3]. Crossing the epithelial barrier by adhering to and invading intestinal epithelial cells gives access to internal organs, the first step toward systemic infection of the host. Bacteriophages (or “phages” for short) are viruses that attack bacteria in a host-specific manner, acting as self-replicating antimicrobials. Lytic phages replicate through the lytic cycle, in which the phage infects the bacterial cell, uses the bacterial replication and translation machinery to replicate, and lyses the bacteria to release new phage particles

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