A comparative genomics approach for identifying host-range determinants in Streptococcus thermophilus bacteriophages

Paula Szymczak,Mariana G Pinho,Martin Holm Rau,Sérgio Raposo Filipe,Finn Kvist Vogensen,João M Monteiro,Thomas Janzen,Ahmad A Zeidan

doi:10.1038/s41598-019-44481-z

Abstract

Comparative genomics has proven useful in exploring the biodiversity of phages and understanding phage-host interactions. This knowledge is particularly useful for phages infecting Streptococcus thermophilus, as they constitute a constant threat during dairy fermentations. Here, we explore the genetic diversity of S. thermophilus phages to identify genetic determinants with a signature for host specificity, which could be linked to the bacterial receptor genotype. A comparative genomic analysis was performed on 142 S. thermophilus phage genomes, 55 of which were sequenced in this study. Effectively, 94 phages were assigned to the group cos (DT1), 36 to the group pac (O1205), six to the group 5093, and six to the group 987. The core genome-based phylogeny of phages from the two dominating groups and their receptor binding protein (RBP) phylogeny corresponded to the phage host-range. A role of RBP in host recognition was confirmed by constructing a fluorescent derivative of the RBP of phage CHPC951, followed by studying the binding of the protein to the host strain. Furthermore, the RBP phylogeny of the cos group was found to correlate with the host genotype of the exocellular polysaccharide-encoding operon. These findings provide novel insights towards developing strategies to combat phage infections in dairies.

Highlights

Bacteriophages represent a constant threat for the dairy industry worldwide
The overall objective of this study is to investigate the genetic diversity of a S. thermophilus phage population to identify genetic determinants with a signature for host specificity, which could be linked to the receptor genotype in bacteria
Four groups of S. thermophilus phages were defined, and additional subgroups were observed within the two dominating groups, known as cos and pac

Summary

Introduction

Bacteriophages represent a constant threat for the dairy industry worldwide. Infections of the bacterial starters with phages result in acidification failures, frequently leading to a lower quality of dairy products[1]. Genomic studies provide insights into the evolution and relatedness of phages, rendering fast and precise phage taxonomic schemes These studies are useful to elucidate mechanisms of phage-host interactions, and this knowledge is essential for the rational design of novel anti-phage strategies[1,5]. Such efforts include designing PCR methods for phage monitoring[6,7,8,9], tracking the dynamics of the phage community during dairy fermentations[10], identifying groups of genes with host-specificity signatures[11], or optimizing starter rotation schemes by selecting phage-unrelated strains[12,13]. RBP genes in the 987- and 5093-group phages were established by expressing and purifying phage proteins, followed by studying the inhibitory effect of these proteins on phage adsorption to the host strain[9,17]

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Conclusion