Quantification of lysogeny caused by phage coinfections in microbial communities from biophysical principles

Abstract

Temperate phages can integrate in their bacterial host genome to form a lysogen, often modifying the phenotype of the host. Lysogens are dominant in the microbial-dense environment of the mammalian-gut. This observation contrasts with the long-standing hypothesis of lysogeny being favored in microbial communities with low densities. Here we hypothesized that phage coinfections--the most studied molecular mechanism of lysogeny in lambda phage--increases at high microbial abundances. To test this hypothesis, we developed a biophysical model of coinfection and stochastically sampled ranges of phage and bacterial concentrations, adsorption rates, lysogenic commitment times, and community diversity from marine and gut microbiomes. Based on lambda experiments, a Poisson process assessed the probability of lysogeny via coinfection in these ecosystems. In 90% of the sampled marine ecosystems, lysogeny stayed below 10% of the bacterial community. In contrast, 25% of the sampled gut communities stayed above 25% of lysogeny, representing an estimated nine trillion lysogens formed via phage coinfection in the human gut every day. The prevalence of lysogeny in the gut was a consequence of the higher densities and faster adsorption rates. In marine communities, which were characterized by lower densities and phage adsorption rates, lysogeny via coinfection was still possible for communities with long lysogenic commitments times. Our study suggests that physical mechanisms can favor coinfection and cause lysogeny at poor growth conditions (long commitment times) and in rich environments (high densities and adsorption rates). ImportancePhage integration in bacterial genomes manipulate microbial dynamics from the oceans to the human gut. This phage-bacteria interaction, called lysogeny, is well-studied in laboratory models, but its environmental drivers remain unclear. Here we quantified the frequency of lysogeny via phage coinfection--the most studied mechanism of lysogeny--by developing a biophysical model that incorporated a meta-analysis of the properties of marine and gut microbiomes. Lysogeny was found to be more frequent in high-productive environments like the gut, due to higher phage and bacterial densities and faster phage adsorption rates. At low cell densities, lysogeny via coinfection was possible for hosts with long duplication times. Our research bridges the molecular understanding of lysogeny with the ecology of complex microbial communities.