Cell fate decisions emerge as phages cooperate or compete inside their host

Abstract

The system of the bacterium Escherichia coli and its virus, bacteriophage lambda, is paradigmatic for gene regulation in cell-fate development, yet insight about its mechanisms and complexities are limited due to insufficient resolution of study. Here we develop a 4-colour fluorescence reporter system at the single-virus level, combined with computational models to unravel both the interactions between phages and how individual phages determine cellular fates. We find that phages cooperate during lysogenization, compete among each other during lysis, and that confusion between the two pathways occasionally occurs. Additionally, we observe that phage DNAs have fluctuating cellular arrival times and vie for resources to replicate, enabling the interplay during different developmental paths, where each phage genome may make an individual decision. These varied strategies could separate the selection for replication-optimizing beneficial mutations during lysis from sequence diversification during lysogeny, allowing rapid adaptation of phage populations for various environments.

Ecological and Evolutionary Benefits of Temperate Phage: What Does or Doesn't Kill You Makes You Stronger

“…[65] Thus, more trigger-happy prophages gain a reproductive advantage during lysis. [66,67] Such conflict over lysis timing could potentially drive a coevolutionary arms race for ever-more sensitive induction among co-infecting temperate phages. 3.…”

Fluorescent nanodiamond‐bacteriophage conjugates maintain host specificity

“…To assess the efficiency of FND complexing with phage particles, we chose to biotinylate a phage carrying a fluorescent D gene (λLZ1476). This phage, established in our previous work, allows us to observe individual phages with fluorescence microscopy (Figure d) (Trinh, Szekely, Shao, Balazsi, & Zeng, ). Thus both the phages (Figure d) and FNDs (Figure e) could be visualized at the same magnification with different filter cubes (Yu et al, ).…”

“…In order to act as a tool to identify bacteria, the FND‐phages must retain their ability to bind to their host cells, so we assayed whether the FND‐phages adsorb to E. coli cells using fluorescence microscopy. Lambda‐sensitive host cells were incubated with FND‐phages for 5 min at 35 °C, washed of free virions by centrifugation, and then visualized by fluorescence microscopy (Figures a and b) (Trinh et al, ). We observed FND signals on host cells, where some cells have multiple FND foci (44 FND labeled cells of 108 cells observed); most of these individual FND foci (48 co‐localized FND/phage foci on cells of 56 FND foci on cells in total) had a corresponding phage focus, suggesting that the actual FND‐phage conjugate is bound to the cells (Figure b).…”

The mobility of packaged phage genome controls ejection dynamics

“…enzyme activity, protein synthesis, preservation of ribosome and nucleic acid structures) (Coates, 2010; Rodgers, 1964; Morgan et al, 1966; Lusk et al, 1968) and the phage λ infectious cycle (Fry, 1959; Gaussier et al, 2006). It has been shown that a concentration of ∼5–10 mM of Mg 2+ ions in the extracellular solution is critically important for both optimum adsorption of phage λ (Fry, 1959) to E. coli , as well as phage replication rate (Mackay and Bode, 1976; Harrison and Bode, 1975).…”