Abstract

Background Salmonella enterica subspecies enterica serovar Typhimurium is a Gram-negative pathogen causing salmonellosis. Salmonella Typhimurium-targeting bacteriophages have been proposed as an alternative biocontrol agent to antibiotics. To further understand infection and interaction mechanisms between the host strains and the bacteriophages, the receptor diversity of these phages needs to be elucidated.Methodology/Principal FindingsTwenty-five Salmonella phages were isolated and their receptors were identified by screening a Tn5 random mutant library of S. Typhimurium SL1344. Among them, three types of receptors were identified flagella (11 phages), vitamin B12 uptake outer membrane protein, BtuB (7 phages) and lipopolysaccharide-related O-antigen (7 phages). TEM observation revealed that the phages using flagella (group F) or BtuB (group B) as a receptor belong to Siphoviridae family, and the phages using O-antigen of LPS as a receptor (group L) belong to Podoviridae family. Interestingly, while some of group F phages (F-I) target FliC host receptor, others (F-II) target both FliC and FljB receptors, suggesting that two subgroups are present in group F phages. Cross-resistance assay of group B and L revealed that group L phages could not infect group B phage-resistant strains and reversely group B phages could not infect group L SPN9TCW-resistant strain.Conclusions/SignificanceIn this report, three receptor groups of 25 newly isolated S. Typhimurium-targeting phages were determined. Among them, two subgroups of group F phages interact with their host receptors in different manner. In addition, the host receptors of group B or group L SPN9TCW phages hinder other group phage infection, probably due to interaction between receptors of their groups. This study provides novel insights into phage-host receptor interaction for Salmonella phages and will inform development of optimal phage therapy for protection against Salmonella.

Highlights

  • Emergence of antibiotic-resistant pathogens due to abuse of various antibiotics is driving the development of alternative approaches to pathogen control

  • This study provides novel insights into phage-host receptor interaction for Salmonella phages and will inform development of optimal phage therapy for protection against Salmonella

  • Grouping of Bacteriophages Based on their Receptors To determine the host receptors for 25 phages, a Tn5 random mutant library of S

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Summary

Introduction

Emergence of antibiotic-resistant pathogens due to abuse of various antibiotics is driving the development of alternative approaches to pathogen control. Bacteriophages are considered a possible alternative biocontrol agent for bacterial pathogens [1,2]. This approach has advantages including narrow species specificity and safety for human applications [3]. Salmonella is a Gram-negative foodborne pathogen causing 1.4 million cases of salmonellosis including 17,000 hospitalization and 600 deaths every year in US [6,7]. Typhimurium bacteriophages is getting more attractive as an alternative approach in the treatment for antibiotic-resistant pathogens. Salmonella enterica subspecies enterica serovar Typhimurium is a Gram-negative pathogen causing salmonellosis. Salmonella Typhimurium-targeting bacteriophages have been proposed as an alternative biocontrol agent to antibiotics. To further understand infection and interaction mechanisms between the host strains and the bacteriophages, the receptor diversity of these phages needs to be elucidated

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