The genera of bacteriophages and their receptors are the major determinants of host range

Summary The host range of phages is a key to understand their impact on bacterial ecology and evolution. Because of the complexity of phage–host interactions, the variables that determine the breadth of a phage host range remain poorly understood. Here, we propose a novel holistic approach to identify the host range determinants of a new collection of phages infecting Salmonella , isolated from animal, environmental and wastewater samples that were able to infect 58 of the 71 Salmonella strains in our collection. By using a set of statistic approaches (non‐metric dimensional scaling, Bray–Curtis distance, PERMANOVA), we analysed phenotypic (host range on wild‐type and receptor mutants) and genetic data (taxonomic assignment and receptor binding proteins) to evaluate the impact of isolation strain and niche, phage receptor and genus on the host range. Statistical analysis revealed that two phage characteristics influence the host range by explaining the most variance: the receptor by 45% and the genus by 51%. Interestingly, phage genus and receptor in combination explained 79% of the variance, establishing these characteristics as the major determinants of the host range. This study demonstrates the power and the novelty of applying statistical approaches to phenotypic and genetic data to investigate the ecology of phage–host interactions.