What’s on a prophage: analysis of Salmonella spp. prophages identifies a diverse range of cargo with multiple virulence- and metabolism-associated functions

Abstract

ABSTRACT The gain of mobile elements, such as prophages, can introduce cargo to the recipient bacterium that could facilitate its persistence in or expansion to a new environment, such as a host. While previous studies have focused on identifying and characterizing the genetic diversity of prophages, analyses characterizing the cargo that prophages carry have not been extensively explored. We characterized prophage regions from 303 Salmonella spp. genomes (representing 254 unique serovars) to assess the distribution of prophages in diverse Salmonella . On average, prophages accounted for 3.7% (0.1%–8.8%) of the total genomic content of each isolate. Prophage regions annotated as Gifsy 1 and Salmon Fels 1 were the most commonly identified intact prophages, suggesting that they are common throughout the Salmonella genus. Among 21,687 total coding sequences (CDSs) from intact prophage regions in subsp. enterica genomes, 7.5% (median; range: 1.1%–47.6%) were categorized as having a function not related to prophage integration or phage structure, some of which could potentially provide a functional attribute to the host Salmonella cell. These predicted functions could be broadly categorized into CDSs involved in: (i) modification of cell surface structures (i.e., glycosyltransferases); (ii) modulation of host responses (e.g., SodC/SodA, SopE, ArtAB, and typhoid toxin); (iii) conferring resistance to heavy metals and antimicrobials; (iv) metabolism of carbohydrates, amino acids, and nucleotides; and (v) DNA replication, repair, and regulation. Overall, our systematic analysis of prophage cargo highlights a broader role for prophage cargo in influencing the metabolic, virulence, and resistance characteristics of Salmonella . IMPORTANCE Lysogenic bacteriophages (phages) can integrate their genome into a bacterial host's genome, potentially introducing genetic elements that can affect the fitness of the host bacterium. The functions of prophage-encoded genes are important to understand as these genes could be mobilized and transferred to a new host. Using a large genomic dataset representing >300 isolates from all known subspecies and species of Salmonella , our study contributes important new findings on the distribution of prophages and the types of cargo that diverse Salmonella prophages carry. We identified a number of coding sequences (CDSs) annotated as having cell surface-modifying attributes, suggesting that prophages may have played an important role in shaping Salmonella 's diverse surface antigen repertoire. Furthermore, our characterization of prophages suggests that they play a broader role in facilitating the acquisition and transfer of CDSs associated with metabolism, DNA replication and repair, virulence factors, and to a lesser extent, antimicrobial resistance.