Receptor Diversity and Host Interaction of Bacteriophages Infecting <em>Salmonella enterica</em> Serovar Typhimurium

<div><h3>Background</h3><p><em>Salmonella enterica</em> subspecies <em>enterica</em> serovar Typhimurium is a Gram-negative pathogen causing salmonellosis. <em>Salmonella</em> 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.</p> <h3>Methodology/Principal Findings</h3><p>Twenty-five <em>Salmonella</em> 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 <em>Siphoviridae</em> family, and the phages using O-antigen of LPS as a receptor (group L) belong to <em>Podoviridae</em> 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.</p> <h3>Conclusions/Significance</h3><p>In this report, three receptor groups of 25 newly isolated <em>S.</em> 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 <em>Salmonella</em> phages and will inform development of optimal phage therapy for protection against <em>Salmonella</em>.</p>