In silico Evolution of Lysis-Lysogeny Strategies Reproduces Observed Lysogeny Propensities in Temperate Bacteriophages

Abstract

Bacteriophages are the most abundant organisms on the planet and both lytic and temperate phages play key roles as shapers of ecosystems and drivers of bacterial evolution. Temperate phages can choose between (i) lysis: exploiting their bacterial hosts by producing multiple phage particles and releasing them by lysing the host cell, and (ii) lysogeny: establishing a potentially mutually beneficial relationship with the host by integrating their chromosome into the host cell's genome. Temperate phages exhibit lysogeny propensities in the curiously narrow range of 5–15%. For some temperate phages, the propensity is further regulated by the multiplicity of infection, such that single infections go predominantly lytic while multiple infections go predominantly lysogenic. We ask whether these observations can be explained by selection pressures in environments where multiple phage variants compete for the same host. Our models of pairwise competition, between phage variants that differ only in their propensity to lysogenize, predict the optimal lysogeny propensity to fall within the experimentally observed range. This prediction is robust to large variation in parameters such as the phage infection rate, burst size, decision rate, as well as bacterial growth rate, and initial phage to bacteria ratio. When we compete phage variants whose lysogeny strategies are allowed to depend upon multiplicity of infection, we find that the optimal strategy is one which switches from full lysis for single infections to full lysogeny for multiple infections. Previous attempts to explain lysogeny propensity have argued for bet-hedging that optimizes the response to fluctuating environmental conditions. Our results suggest that there is an additional selection pressure for lysogeny propensity within phage populations infecting a bacterial host, independent of environmental conditions.

Evolutionary stability of the lysis‐lysogeny decision: why be virulent?

“…Stewart and Levin demonstrated broad conditions under which temperate and lytic phages could coexist, and offered two likely explanations for the prevalence of lysogeny: (i) in spatially structured environments, lysogenic colonies are resistant to diffusing phage, and (ii) if the host cell population oscillates, lysogeny is favored when the host population drops below the minimum density required to support a lytic phage population. Lysogeny can also be favored as a bet-hedging strategy in the face of harsh environmental conditions that would eliminate free phage while leaving viable host cells (Avlund et al 2009;Maslov and Sneppen 2015), or when susceptible hosts are completely exhausted by the phage (Sinha et al 2017). Recent experimental and theoretical work has demonstrated that lysis (virulence) is favored when susceptible hosts are abundant, while lysogeny is favored when transmission is limited by available host cells or by spatial structure (Berngruber et al 2013(Berngruber et al , 2015.…”

Estimating Optimal Lysogenic Propensity for Viruses in Stressed Environments

“…The lyso-9 genic option makes it possible for phages to survive in the event of depletion 10 of host bacterial cells. Previous studies on phage-host interaction have shown 11 that the fraction of infected bacterial cells undergoing lysogeny is dependent 12 on multiple factors including, but not limited to multiplicity of infection [6], [7] 13 and environmental stresses [6], [8], [9]. Phages analyzed in these studies have 14 been observed to opt for lysogeny more often when the multiplicity of infection 15 is higher.…”

“…18 19 Understanding the logic behind the lysis-lysogeny decision is important in 20 order to comprehend how the phages are able to coexist with their hosts despite 21 their high burst rates. A number of theoretical models [5], [10], [11], [12] have 22 been proposed to explain the observed experimental trends. Although these 23 models do provide a possible understanding of the system, they have their own 24 limitations.…”

“…Avlund et al use the analogy of single player and 27 multi-player games to explain the difference in results for M oI values of 1 and 28 2, and the use of discrete values of M oI is attributed to the fact that phages 29 can assess only the number of phages in the cell they have infected. Sinha et 30 al [11] model the effect of various factors -such as initial phage and bacterial 31 populations, the burst size, the infection rate, and the bacterial growth rate -on 32 the lysogenic propensity. The authors calculate the optimal lysogenic propensity 33 by allowing different propensities to compete against each other under different 34 system parameters.…”

“…15, 2018; -shown by the red curve with an extremely small error area. Classically, en-172 vironments have been assumed to be good [11], [24], thus missing out on the 173 variation caused by changes in the values of the parameters in bad environments. 174 It is interesting to note that as the environment becomes worse for phages, the 175 lysogenic propensity at a given M oI decreases.…”