Salmonella enterica Prophage Sequence Profiles Reflect Genome Diversity and Can Be Used for High Discrimination Subtyping

Abstract

Non-typhoidal <i>Salmonella</i> is a leading cause of foodborne illness worldwide. Prompt and accurate identification of the sources of <i>Salmonella</i> responsible for disease outbreaks is crucial to minimize infections and eliminate ongoing sources of contamination. Current subtyping tools including single nucleotide polymorphism (SNP) typing may be inadequate, in some instances, to provide the required discrimination among epidemiologically unrelated <i>Salmonella</i> strains. Prophage genes represent the majority of the accessory genes in bacteria genomes and have potential to be used as high discrimination markers in <i>Salmonella</i>. In this study, the prophage sequence diversity in different <i>Salmonella</i> serovars and genetically related strains was investigated. Using whole genome sequences of 1,760 isolates of <i>S. enterica</i> representing 151 <i>Salmonella</i> serovars and 66 closely related bacteria, prophage sequences were identified from assembled contigs using PHASTER. We detected 154 different prophages in <i>S. enterica</i> genomes. Prophage sequences were highly variable among <i>S. enterica</i> serovars with a median ± interquartile range (IQR) of 5 ± 3 prophage regions per genome. While some prophage sequences were highly conserved among the strains of specific serovars, few regions were lineage specific. Therefore, strains belonging to each serovar could be clustered separately based on their prophage content. Analysis of <i>S</i>. Enteritidis isolates from seven outbreaks generated distinct prophage profiles for each outbreak. Taken altogether, the diversity of the prophage sequences correlates with genome diversity. Prophage repertoires provide an additional marker for differentiating <i>S. enterica</i> subtypes during foodborne outbreaks.