Host Resistance, Genomics and Population Dynamics in a Salmonella Enteritidis and Phage System.

Angela Holguín,Guilherme Oliveira,Camila Buitrago,Frank Møller Aarestrup,Pimlapas Leekitcharoenphon,Viviana Clavijo,Catalina Prada-Peñaranda,Laura Rabelo Leite,Martha Vives,Pablo Cárdenas

doi:10.3390/v11020188

Abstract

Bacteriophages represent an alternative solution to control bacterial infections. When interacting, bacteria and phage can evolve, and this relationship is described as antagonistic coevolution, a pattern that does not fit all models. In this work, the model consisted of a microcosm of Salmonella enterica serovar Enteritidis and φSan23 phage. Samples were taken for 12 days every 48 h. Bacteria and phage samples were collected; and isolated bacteria from each time point were challenged against phages from previous, contemporary, and subsequent time points. The phage plaque tests, with the genomics analyses, showed a mutational asymmetry dynamic in favor of the bacteria instead of antagonistic coevolution. This is important for future phage-therapy applications, so we decided to explore the population dynamics of Salmonella under different conditions: pressure of one phage, a combination of phages, and phages plus an antibiotic. The data from cultures with single and multiple phages, and antibiotics, were used to create a mathematical model exploring population and resistance dynamics of Salmonella under these treatments, suggesting a nonlethal, growth-inhibiting antibiotic may decrease resistance to phage-therapy cocktails. These data provide a deep insight into bacterial dynamics under different conditions and serve as additional criteria to select phages and antibiotics for phage-therapy.

Highlights

-called “superbugs,” or bacteria resistant to multiple antibiotics, are a worldwide problem that urgently requires solutions in order to control bacterial infections
The AcrAB-TolC efflux pump system found in different Enterobacteriaceae can transport multiple antibiotics, including chloramphenicol, across both the inner and outer membrane, and have been found to be involved in resistance to these compounds [23,24,25]
We selected key genes related to bacterial phage-resistance mechanisms, and we modeled the interaction of candidate receptors and tail fiber proteins using DockingServer [34,35]

Summary

Introduction

-called “superbugs,” or bacteria resistant to multiple antibiotics, are a worldwide problem that urgently requires solutions in order to control bacterial infections. Phages were used as a therapy for a few years until penicillin was discovered. Following the advent of antibiotics, Western countries halted research on phages, and antibiotics were used widely until a few years ago when reports on bacterial resistance increased, and the world started to look for alternatives [1]. Viruses 2019, 11, 188 phages emerged once again, and several studies have been conducted to understand phage–bacteria interaction and the applicability of these in food, animals, and humans [1]. Salmonella was chosen as a model due to the problem it represents for public health in the world and other countries. This bacterium causes salmonellosis, a form of food poisoning in humans

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Results

Conclusion