Molecular and Evolutionary Determinants of Bacteriophage Host Range

The host range of a bacteriophage is the taxonomic diversity of hosts it can successfully infect. Host range, one of the central traits to understand in phages, is determined by a range of molecular interactions between phage and host throughout the infection cycle. While many well studied model phages seem to exhibit a narrow host range, recent ecological and metagenomics studies indicate that phages may have specificities that range from narrow to broad. There is a growing body of studies on the molecular mechanisms that enable phages to infect multiple hosts. These mechanisms, and their evolution, are of considerable importance to understanding phage ecology and the various clinical, industrial, and biotechnological applications of phage. Here we review knowledge of the molecular mechanisms that determine host range, provide a framework defining broad host range in an evolutionary context, and highlight areas for additional research. Broad-host-range phages are more common in nature than previously thought, and most environments have a variety of narrow-range and broad-host-range phages. In phenotypic broad-host-range phages, individual phage particles can infect multiple hosts. In genotypic broad-host-range phages, individual particles infect only one host, but specific mutations enable rapid host switching between generations, leading to a broad-host-range quasispecies. Broad-host-range phages, engineered or natural, are useful for treating multiple-strain infections, but phage therapy is dependent on a full understanding of host-range evolution. The widespread existence of narrow-host-range phages among those studied is at least partly caused by biases in phage-isolation methods. Ecological parameters, such as host density and host diversity, probably determine the likelihood and richness of broad-host-range phages in a given environment.