Resolving the structure of phage–bacteria interactions in the context of natural diversity

Abstract

Microbial communities are shaped by viral predators. Yet, resolving which viruses (phages) and bacteria are interacting is a major challenge in the context of natural levels of microbial diversity. Thus, fundamental features of how phage-bacteria interactions are structured and evolve in the wild remain poorly resolved. Here we use large-scale isolation of environmental marine Vibrio bacteria and their phages to obtain estimates of strain-level phage predator loads, and use all-by-all host range assays to discover how phage and host genomic diversity shape interactions. We show that lytic interactions in environmental interaction networks (as observed in agar overlay) are sparse—with phage predator loads being low for most bacterial strains, and phages being host-strain-specific. Paradoxically, we also find that although overlap in killing is generally rare between tailed phages, recombination is common. Together, these results suggest that recombination during cryptic co-infections is an important mode of phage evolution in microbial communities. In the development of phages for bioengineering and therapeutics it is important to consider that nucleic acids of introduced phages may spread into local phage populations through recombination, and that the likelihood of transfer is not predictable based on lytic host range.

Genetic determinants of host tropism inKlebsiellaphages

“…Our results suggest that tail spike domain swapping is frequent in nature, even across viral families. As a result, phage taxonomy was a poor predictor of host tropism, in contrast to some previous findings (Gencay et al, 2019; Sørensen et al, 2021) but agrees with recent work showing that phage host range is largely independent of phage taxonomy (Göller et al, 2021) or morphotype (Kauffman et al, 2022). Our results hint at the possibility of predicting phage capsular tropism only from depolymerase sequence information, a goal that we achieved partially and that should be further addressed in the future.…”

“…Here, we have performed a thorough analysis of the interactions between K. pneumoniae and its phages, using a larger phage-host interaction matrix than in previous studies (de Sousa et al, 2020; Townsend et al, 2021; Venturini et al, 2020). All the analyzed phages but one were novel and encompassed different families and undescribed taxonomical entities (Herridge et al, 2020), showing the importance of carrying out more extensive samplings to uncover the phage diversity (Göller et al, 2021; Kauffman et al, 2022; Maffei et al, 2021).…”

“…Typically, a phage infects only a subset of strains of a given bacterial species (de Jonge et al, 2019). However, some phages can infect different bacterial species (Göller et al, 2021; Kauffman et al, 2022) or even distinct genera (Gambino et al, 2020; Hamdi et al, 2017). Available tools can predict phages’ host range with moderately good accuracies at the family and genus levels, but perform worse at lower taxonomical ranks (Coutinho et al, 2021; Villarroel et al, 2016; Young et al, 2020).…”

Phage–host coevolution in natural populations

“…To identify the putative mechanisms operating in the bacteria to block phage infection we used Defense-Finder 24 . This revealed a wealth of different known systems, such as the restriction modification systems 6 R-M type I (200), type IV (51), the DNA phosphorothioation-based defence system Dnd 25 (51) and diverse systems involved in abortive infection 26 (Fig. 4a).…”

The evolution of a counter-defense mechanism in a virus constrains its host range

“…As our experimental evolution demonstrates, if selection to infect a host and overcome its defense systems is not maintained, the corresponding anti-defense genes, which are not essential for phage replication, can be lost following pressure to infect new and different hosts (Figure 7). Such genome dynamics, which stem from the relentless coevolution of phage with their hosts, may help to explain the staggering diversity of accessory genes within phage genomes (Pope et al, 2015) and their sometimes narrow host ranges across hosts with varied and dynamic immune profiles (Hussain et al, 2021; Kauffman et al, 2022).…”