Minimal Gene Regulatory Circuits that Can Count like Bacteriophage Lambda

Avlund, Mikkel; Dodd, Ian B.; Sneppen, Kim; Krishna, Sandeep

doi:10.1016/j.jmb.2009.09.053

Cited by 14 publications

(34 citation statements)

References 62 publications

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“…The lysis-lysogeny decision in wt is, for example, dependent on the multiplicity of infection (MOI) (32,33). For an MOI of 1 (only one phage infects the bacterium), the phage nearly always chooses lysis, whereas infections with an MOI of Ͼ1 (two or more phages infect the same bacterium in the same small time window before the decision is made) allow a substantial fraction to choose lysogeny (54)(55)(56)(57).…”

Section: Resultsmentioning

confidence: 99%

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Population Dynamics of Phage and Bacteria in Spatially Structured Habitats Using Phage λ and Escherichia coli

2016

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Bacteria living in physically structured habitats are exposed heterogeneously to both resources and different types of phages. While there have been numerous experimental approaches to examine spatially distributed bacteria exposed to phages, there is little theory to guide the design of these experiments, interpret their results, or expand the inferences drawn to a broader ecological and evolutionary context. Plaque formation provides a window into understanding phage-bacterium interactions in physically structured populations, including surfaces, semisolids, and biofilms. We develop models to address the plaque dynamics for a temperate phage and its virulent mutants. The models are compared with phage -Escherichia coli system to quantify their applicability. We found that temperate phages gave an increasing number of gradually smaller colonies as the distance increased from the plaque center. For low-lysogen frequency this resulted in plaques with most of the visible colonies at an intermediate distance between the center and periphery. Using spot inoculation, where phages in excess of bacteria were inoculated in a circular area, we measured the frequency and spatial distribution of lysogens. The spot morphology of cII-negative (cII ؊ ) and cIII ؊ mutants of phage displays concentric rings of high-density lysogenic colonies. The simplest of these ring morphologies was reproduced by including multiplicity of infection (MOI) sensitivity in lysis-lysogeny decisions, but its failure to explain the occasional observation of multiple rings in cIII ؊ mutant phages highlights unknown features of this phage. Our findings demonstrated advantages of temperate phages over virulent phages in exploiting limited resources in spatially distributed microbial populations. IMPORTANCEPhages are the most abundant organisms on earth, and yet little is known about how phages and bacterial hosts are influencing each other in density and evolution. Phages can be either virulent or temperate, a difference that is highlighted when a spatially structured bacterial population is infected. Phage is a temperate phage, with a capacity for dormancy that can be modified by single gene knockouts. The stochastic bias in the lysis-lysogeny decision's probability is reflected in plaque morphologies on bacterial lawns. We present a model for plaque morphology of both virulent and temperate phages, taking into account the underlying survival of bacterial microcolonies. It reproduces known plaque morphologies and speaks to advantages of temperate phages in a spatially structured environment. T he active biomass on earth is dominated by prokaryotes, which constitute about half the amount of the carbon stored in living organisms (1). Bacteria are widely exposed to phages, which in turn are the most numerous inhabitants of our biosphere (2, 3). Phages have developed a diversity of behaviors that support their survival (survival strategies), which continues to inform our understanding of evolution and gene editing (4-8). One classical phage type ...

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Section: Resultsmentioning

confidence: 99%

“…Scale bar, 1 mm. For the influence of mutants on the phage regulatory network see, e.g., the work of Avlund et al and Trusina et al (56,63). adsorption mixes were cast as soft-agar overlays in F-top agar (48) supplemented with 10 mM MgCl 2 .…”

Section: Figmentioning

confidence: 99%

Population Dynamics of Phage and Bacteria in Spatially Structured Habitats Using Phage λ and Escherichia coli

2016

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“…In the lysogenic cycle, most of the phage genes are silenced and the phage genome replicates together with that of the host cell. The lysis-lysogeny decision is regulated by bistable genetic switches (Dodd et al, 1990; Ptashne, 2004; Oppenheim et al, 2005; Avlund et al, 2009a). In the presence of inevitable noise, this typically results in stochastic behavior characterized by a certain lysogeny propensity, i.e., each infected cell has a certain probability to go lysogenic.…”

Section: Introductionmentioning

confidence: 99%

“…A large variety of bistable genetic switches have evolved in nature. Moreover, theoretical studies suggest that such switches can be implemented in many different ways and function in different parameter regimes (Avlund et al, 2009a, 2010). However, observations under laboratory conditions suggest that the lysogeny propensity lies in a narrow range, around 5 to 15%, for a wide range of temperate phage species (Hong et al, 1971; Kourilsky, 1973; Ikeuchi and Kurahashi, 1978; Schubert et al, 2007; Maynard et al, 2010; Broussard et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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.

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“…Furthermore, we have a limited knowledge of the biology of phages in the context of selective pressures phages encounter outside of a laboratory setting. However, as our knowledge of the ecology of phages and the types of natural genetic switches expands, and as efforts to engineer synthetic genetic switches leads to new insights, 28 - 30 our understanding of how complex genetic circuits evolve and the variety of circuitries possible will be greatly enhanced. This will further allow us to control gene expression to a level of sophistication that will open many possibilities for research, medical and industrial use of finely tuned genetic switches.…”

Section: Discussionmentioning

confidence: 99%

Evolution of genetic switch complexity

Broussard

Hatfull

2013

Bacteriophage

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The circuitry of the phage λ genetic switch determining the outcome of lytic or lysogenic growth is well-integrated and complex, raising the question as to how it evolved. It is plausible that it arose from a simpler ancestral switch with fewer components that underwent various additions and refinements, as it adapted to vast numbers of different hosts and conditions. We have recently identified a new class of genetic switches found in mycobacteriophages and other prophages, in which immunity is dependent on integration. These switches contain only three genes (integrase, repressor and cro) and represent a major departure from the λ-like circuitry, lacking many features such as xis, cII and cIII. These small self-contained switches represent an unrealized, elegant circuitry for controlling infection outcome. In this addendum, we propose a model of possible events in the evolution of a complex λ-like switch from a simpler integration-dependent switch.

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Minimal Gene Regulatory Circuits that Can Count like Bacteriophage Lambda

Cited by 14 publications

References 62 publications

Population Dynamics of Phage and Bacteria in Spatially Structured Habitats Using Phage λ and Escherichia coli

Population Dynamics of Phage and Bacteria in Spatially Structured Habitats Using Phage λ and Escherichia coli

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

Evolution of genetic switch complexity

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