Characterization of Listeria Bacteriophages and mutant Listeria monocytogenes for the study of resistance mechanisms

Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen widely detected in contaminated food, threatening food safety. Consumption of food that contains L. monocytogenes may lead to fatal listeriosis. In all thirteen serotypes of L. monocytogenes, serotype 1/2a is responsible for the most food contamination cases, and serotype 4b accounts for the most clinic disease. With the widespread emergence of antibiotic resistant bacteria, using bacteriophages (phages) to biocontrol pathogens in food and the food processing environment becomes a promising way to protect food from contamination in the food industry. However, the effect of Listeria phages is limited by the appearance of phage resistant mutants. The purpose of this study is to study the interplay between Listeria monocytogenes and Listeria phages, especially the resistance mechanisms developed by resistant mutant strains. Rhamnose is an essential receptor for many phages which infect L. monocytogenes, and rhamnose deficient mutants can avoid infection from most Listeria phages except for LP-018 from a collection of 120 phages. The characteristics of LP-018 were studied, and a resistance mechanism independent of adsorption inhibition was identified. To increase the diversity of characterized phages, wild phages that target serotype 4b strains were also identified and characterized. Co-evolution experiments between bacteriophages and Listeria monocytogenes serotype 1/2a and 4b were also conducted to develop a diversity of mutant strains to study resistance mechanisms.