Switches in Bacteriophage Lambda Development

Oppenheim, Amos B.; Kobiler, Oren; Stavans, Joel; Court, Donald L.; Adhya, Sankar

doi:10.1146/annurev.genet.39.073003.113656

Cited by 414 publications

(504 citation statements)

References 103 publications

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“…S9 A and B and SI Results). The intergenic region upstream of cI in phage lambda is an extremely well-studied transcriptional regulatory region; the right operator (O R ) with its three sites that competitively bind the repressor and Cro proteins, constitutes a carefully regulated switch between lysogenic and lytic cycles (23,24). Upon RecA activation, the repressor is cleaved and the prophage is induced (25).…”

Section: Nonsimultaneous Detection Of Viruses and Community Rearrangementioning

confidence: 99%

Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut

Reyes

McNulty

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

299

269

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Bacterial viruses (phages) are the most abundant biological group on Earth and are more genetically diverse than their bacterial prey/ hosts. To characterize their role as agents shaping gut microbial community structure, adult germ-free mice were colonized with a consortium of 15 sequenced human bacterial symbionts, 13 of which harbored one or more predicted prophages. One member, Bacteroides cellulosilyticus WH2, was represented by a library of isogenic transposon mutants that covered 90% of its genes. Once assembled, the community was subjected to a staged phage attack with a pool of live or heat-killed virus-like particles (VLPs) purified from the fecal microbiota of five healthy humans. Shotgun sequencing of DNA from the input pooled VLP preparation plus shotgun sequencing of gut microbiota samples and purified fecal VLPs from the gnotobiotic mice revealed a reproducible nonsimultaneous pattern of attack extending over a 25-d period that involved five phages, none described previously. This system allowed us to (i) correlate increases in specific phages present in the pooled VLPs with reductions in the representation of particular bacterial taxa, (ii) provide evidence that phage resistance occurred because of ecological or epigenetic factors, (iii) track the origin of each of the five phages among the five human donors plus the extent of their genome variation between and within recipient mice, and (iv) establish the dramatic in vivo fitness advantage that a locus within a B. cellulosilyticus prophage confers upon its host. Together, these results provide a defined community-wide view of phage-bacterial host dynamics in the gut.T he human gut is home to tens of trillions of microbial cells representing all three domains of life, although most are bacteria. These organisms collaborate and compete for functional niches and physical locations (habitats). Together, they form a continuously functioning microbial metabolic "organ." The microbial diversity, interpersonal variation, and dynamism of the human gut microbiota make the task of identifying the factors that define community configurations extremely challenging.In some ecosystems, phages maintain high bacterial strain level diversity through lysis of their host strains (constant diversity dynamics model; refs 1, 2). The resulting emptied niche is filled with either an evolved resistant bacterial strain or a taxonomically closely related bacterial species. These dynamics have been observed in open marine environments (1). In contrast, a recent study of 37 healthy adults indicated that a person's fecal microbiota was remarkably stable, with 60% of bacterial strains retained over the course of 5 y (3). Stability followed a power law dynamic that when extrapolated suggests that most strains in an individual's gut community are retained for decades (3). In a metagenomic analysis of virus-like particles (VLPs) purified from the fecal microbiota of healthy adult monozygotic twins and their mothers, sampled over the course of a year, viral community structure exh...

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Section: Nonsimultaneous Detection Of Viruses and Community Rearrangementioning

confidence: 99%

Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut

Reyes

McNulty

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

299

269

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“…This result was obtained by stochastic simulation of reaction set (1) using the Gillespie algorithm [38,39]. This algorithm generates a continuous time Markov process which is exactly described by the master equation (10). For a given switch state, the number n of molecules of R varies according to reactions (1a).…”

Section: The Modelmentioning

confidence: 99%

“…Such networks are known as bistable genetic switches: they have two possible long-time states, corresponding to alternative phenotypic states. Well-known examples are the switch controlling the transition from the lysogenic to lytic states in bacteriophage λ [9,10], and the lactose utilisation network of the bacterium Escherichia coli [11]. Several simple mechanisms for achieving bistability have been studied, including pairs of mutually repressing genes [12,13], positive feedback loops [14] and mixed feedback loops [15].…”

Section: Introductionmentioning

confidence: 99%

Statistical physics of a model binary genetic switch with linear feedback

Visco

Allen²,

Evans³

2009

Phys. Rev. E

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We study the statistical properties of a simple genetic regulatory network that provides heterogeneity within a population of cells. This network consists of a binary genetic switch in which stochastic flipping between the two switch states is mediated by a "flipping" enzyme. Feedback between the switch state and the flipping rate is provided by a linear feedback mechanism: the flipping enzyme is only produced in the on switch state and the switching rate depends linearly on the copy number of the enzyme. This work generalises the model of [Phys. Rev. Lett., 101, 118104] to a broader class of linear feedback systems. We present a complete analytical solution for the steady-state statistics of the number of enzyme molecules in the on and off states, for the general case where the enzyme can mediate flipping in either direction. For this general case we also solve for the flip time distribution, making a connection to first passage and persistence problems in statistical physics. We show that the statistics of the model are non-Poissonian, leading to a peak in the flip time distribution. The occurrence of such a peak is analysed as a function of the parameter space. We present a new relation between the flip time distributions measured for two relevant choices of initial condition. We also introduce a new correlation measure to show that this model can exhibit long-lived temporal correlations, thus providing a primitive form of cellular memory. Motivated by DNA replication as well as by evolutionary mechanisms involving gene duplication, we study the case of two switches in the same cell. This results in correlations between the two switches; these can either positive or negative depending on the parameter regime.

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“…Although the expression of this information is controlled at multiple levels, regulation at the level of transcription initiation allows a gene to be controlled at the earliest stage of its expression. The literature is replete with examples of regulatory proteins that control transcription initiation and the history of the field is dominated by examples of proteindependent control mechanisms, such as those controlling the life cycle of bacteriophage lambda or the expression of the lac operon (Lewis 2011;Oppenheim et al 2005;Wilson et al 2007). Research that has focused intensively on protein regulators for more than five decades has pushed the regulatory role of DNA into the background where, at best, it is regarded as contributing to gene control by providing cis-acting sites for the binding of regulatory proteins or through its possession of a structural flexibility that facilitates interactions between bound proteins via DNA looping (Schleif 2013;Semsey et al 2005).…”

Section: Introductionmentioning

confidence: 99%

DNA supercoiling is a fundamental regulatory principle in the control of bacterial gene expression

Dorman

2016

Biophys Rev

107

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Although it has become routine to consider DNA in terms of its role as a carrier of genetic information, it is also an important contributor to the control of gene expression. This regulatory principle arises from its structural properties. DNA is maintained in an underwound state in most bacterial cells and this has important implications both for DNA storage in the nucleoid and for the expression of genetic information. Underwinding of the DNA through reduction in its linking number potentially imparts energy to the duplex that is available to drive DNA transactions, such as transcription, replication and recombination. The topological state of DNA also influences its affinity for some DNA binding proteins, especially in DNA sequences that have a high A + T base content. The underwinding of DNA by the ATP-dependent topoisomerase DNA gyrase creates a continuum between metabolic flux, DNA topology and gene expression that underpins the global response of the genome to changes in the intracellular and external environments. These connections describe a fundamental and generalised mechanism affecting global gene expression that underlies the specific control of transcription operating through conventional transcription factors. This mechanism also provides a basal level of control for genes acquired by horizontal DNA transfer, assisting microbial evolution, including the evolution of pathogenic bacteria.

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Switches in Bacteriophage Lambda Development

Cited by 414 publications

References 103 publications

Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut

Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut

Statistical physics of a model binary genetic switch with linear feedback

DNA supercoiling is a fundamental regulatory principle in the control of bacterial gene expression

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