Use of Bacteriophage Amended with CRISPR-Cas Systems to Combat Antimicrobial Resistance in the Bacterial Foodborne Pathogen Listeria monocytogenes.

Cameron Parsons,Sophia Kathariou,Phillip Brown

doi:10.3390/antibiotics10030308

Cameron Parsons, Sophia Kathariou + Show 1 more

Open Access

https://doi.org/10.3390/antibiotics10030308

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Abstract

Listeria monocytogenes is a bacterial foodborne pathogen and the causative agent of the disease listeriosis, which though uncommon can result in severe symptoms such as meningitis, septicemia, stillbirths, and abortions and has a high case fatality rate. This pathogen can infect humans and other animals, resulting in massive health and economic impacts in the United States and globally. Listeriosis is treated with antimicrobials, typically a combination of a beta-lactam and an aminoglycoside, and L. monocytogenes has remained largely susceptible to the drugs of choice. However, there are several reports of antimicrobial resistance (AMR) in both L. monocytogenes and other Listeria species. Given the dire health outcomes associated with listeriosis, the prospect of antimicrobial-resistant L. monocytogenes is highly problematic for human and animal health. Developing effective tools for the control and elimination of L. monocytogenes, including strains with antimicrobial resistance, is of the utmost importance to prevent further dissemination of AMR in this pathogen. One tool that has shown great promise in combating antibiotic-resistant pathogens is the use of bacteriophages (phages), which are natural bacterial predators and horizontal gene transfer agents. Although native phages can be effective at killing antibiotic-resistant pathogens, limited host ranges and evolved resistance to phages can compromise their use in the efforts to mitigate the global AMR challenge. However, recent advances can allow the use of CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) to selectively target pathogens and their AMR determinants. Employment of CRISPR-Cas systems for phage amendment can overcome previous limitations in using phages as biocontrol and allow for the effective control of L. monocytogenes and its AMR determinants.

Highlights

Listeria monocytogenes is a facultative intracellular bacterial pathogen that is found ubiquitously in the environment and is most frequently transmitted via contaminated food [1,2,3]
Listeriaphages have been approved for use in foods since roughly 2006 [20]
Those equipped with host-targeting clustered regularly interspaced short palindromic repeats (CRISPRs) systems, would likely kill their host at such a rate that they would not account for heritable changes in the bacterial genome

Summary

Introduction

Listeria monocytogenes is a facultative intracellular bacterial pathogen that is found ubiquitously in the environment and is most frequently transmitted via contaminated food [1,2,3]. One potential solution to the problem of antibiotic-resistant L. monocytogenes involves the native predators and horizontal gene transfer agents of this pathogen, namely Listeria-specific bacteriophages (listeriaphages). One of the emerging tools in the fight against antibiotic-resistant bacteria that may prove key to enabling the widespread use of listeriaphages for control of L. monocytogenes, including strains with specific AMR determinants, is the use of clustered regularly interspaced short palindromic repeats (CRISPRs).

Results

Conclusion