Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular level stochastic model for competence cycles in Bacillus subtilis.

ABSTRACT: The role of stochasticity and noise in controlling genetic circuits is investigated in the context of transitions into and from competence in Bacillus subtilis. Recent experiments have demonstrated that bistability is not necessary for this function, but that the existence of one stable fixed point (vegetation) and an excitable unstable one (competence) is sufficient. Stochasticity therefore plays a crucial role in this excitation. Noise can be generated by discrete events such as RNA and protein synthesis and their degradation. We consider an alternative noise source connected with the protein binding/unbinding to the DNA. A theoretical model that includes this "nonadiabatic" mechanism appears to produce a better agreement with experiments than models where only the adiabatic limit is considered, suggesting that this nonconventional stochasticity source may be important for biological functions.

SUBMITTER: Schultz D

PROVIDER: S-EPMC2077070 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Molecular level stochastic model for competence cycles in Bacillus subtilis.

Schultz Daniel D Ben Jacob Eshel E Onuchic José N JN Wolynes Peter G PG

Proceedings of the National Academy of Sciences of the United States of America 20071025 45

The role of stochasticity and noise in controlling genetic circuits is investigated in the context of transitions into and from competence in Bacillus subtilis. Recent experiments have demonstrated that bistability is not necessary for this function, but that the existence of one stable fixed point (vegetation) and an excitable unstable one (competence) is sufficient. Stochasticity therefore plays a crucial role in this excitation. Noise can be generated by discrete events such as RNA and protei ...[more]

PMID: 17962411

Similar Datasets

Stochastic model for Soj relocation dynamics in Bacillus subtilis.

Project description:The Bacillus subtilis Spo0J/Soj proteins, implicated in chromosome segregation and transcriptional regulation, show striking dynamics: Soj undergoes irregular relocations from pole to pole or nucleoid to nucleoid. Here, we report on a mathematical model of the Soj dynamics. Our model, which is closely based on the available experimental data, readily generates dynamic Soj relocations. We show that the irregularity of the relocations may be due to the stochastic nature of the underlying Spo0J/Soj interactions and diffusion. We propose explanations for the behavior of several Spo0J/Soj mutants, including the "freezing" of the Soj dynamics observed in filamentous cells. Our approach underlines the importance of incorporating stochastic effects when modeling spatiotemporal protein dynamics inside cells.

| S-EPMC1174977 | biostudies-literature

Genetic Competence Drives Genome Diversity in Bacillus subtilis.

Project description:Prokaryote genomes are the result of a dynamic flux of genes, with increases achieved via horizontal gene transfer and reductions occurring through gene loss. The ecological and selective forces that drive this genomic flexibility vary across species. Bacillus subtilis is a naturally competent bacterium that occupies various environments, including plant-associated, soil, and marine niches, and the gut of both invertebrates and vertebrates. Here, we quantify the genomic diversity of B. subtilis and infer the genome dynamics that explain the high genetic and phenotypic diversity observed. Phylogenomic and comparative genomic analyses of 42 B. subtilis genomes uncover a remarkable genome diversity that translates into a core genome of 1,659 genes and an asymptotic pangenome growth rate of 57 new genes per new genome added. This diversity is due to a large proportion of low-frequency genes that are acquired from closely related species. We find no gene-loss bias among wild isolates, which explains why the cloud genome, 43% of the species pangenome, represents only a small proportion of each genome. We show that B. subtilis can acquire xenologous copies of core genes that propagate laterally among strains within a niche. While not excluding the contributions of other mechanisms, our results strongly suggest a process of gene acquisition that is largely driven by competence, where the long-term maintenance of acquired genes depends on local and global fitness effects. This competence-driven genomic diversity provides B. subtilis with its generalist character, enabling it to occupy a wide range of ecological niches and cycle through them.

| S-EPMC5765554 | biostudies-literature

Impact of nanoparticles on the Bacillus subtilis (3610) competence.

Project description:Due to the physicochemical properties of nanoparticles, the use of nanomaterials increases every year in industrial and medical processes. At the same time, the increasing number of bacteria becoming resistant to many antibiotics, mostly by a horizontal gene transfer process, is a major public health concern. We herein report, for the first time, the role of nanoparticles in the physiological induction of horizontal gene transfer in bacteria. Besides the most well-known impacts of nanoparticles on bacteria, i.e. death or oxidative stress, two nanoparticles, n-ZnO and n-TiO2, significantly and oppositely impact the transformation efficiency of Bacillus subtilis in biofilm growth conditions, by modification of the physiological processes involved in the induction of competence, the first step of transformation. This effect is the consequence of a physiological adaptation rather than a physical cell injury: two oligopeptide ABC transporters, OppABCDF and AppDFABC, are differentially expressed in response to nanoparticles. Interestingly, a third tested nanoparticle, n-Ag, has no significant effect on competence in our experimental conditions. Overall, these results show that nanoparticles, by altering bacterial physiology and especially competence, may have profound influences in unsuspected areas, such as the dissemination of antibiotic resistance in bacteria.

| S-EPMC5813000 | biostudies-literature

Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis.

Project description:In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off.

| S-EPMC4896167 | biostudies-literature

Agent-based modeling of competence phenotype switching in Bacillus subtilis.

Project description:BackgroundIt is a fascinating phenomenon that in genetically identical bacteria populations of Bacillus subtilis, a distinct DNA uptake phenotype called the competence phenotype may emerge in 10-20% of the population. Many aspects of the phenomenon are believed to be due to the variable expression of critical genes: a stochastic occurrence termed "noise" which has made the phenomenon difficult to examine directly by lab experimentation.MethodsTo capture and model noise in this system and further understand the emergence of competence both at the intracellular and culture levels in B. subtilis, we developed a novel multi-scale, agent-based model. At the intracellular level, our model recreates the regulatory network involved in the competence phenotype. At the culture level, we simulated growth conditions, with our multi-scale model providing feedback between the two levels.ResultsOur model predicted three potential sources of genetic "noise". First, the random spatial arrangement of molecules may influence the manifestation of the competence phenotype. In addition, the evidence suggests that there may be a type of epigenetic heritability to the emergence of competence, influenced by the molecular concentrations of key competence molecules inherited through cell division. Finally, the emergence of competence during the stationary phase may in part be due to the dilution effect of cell division upon protein concentrations.ConclusionsThe competence phenotype was easily translated into an agent-based model - one with the ability to illuminate complex cell behavior. Models such as the one described in this paper can simulate cell behavior that is otherwise unobservable in vivo, highlighting their potential usefulness as research tools.

| S-EPMC3648451 | biostudies-literature

Transformation of environmental Bacillus subtilis isolates by transiently inducing genetic competence.

Project description:Domesticated laboratory strains of Bacillus subtilis readily take up and integrate exogenous DNA. In contrast, "wild" ancestors or Bacillus strains recently isolated from the environment can only be genetically modified by phage transduction, electroporation or protoplast transformation. Such methods are laborious, have a variable yield or cannot efficiently be used to alter chromosomal DNA. A major disadvantage of using laboratory strains is that they have often lost, or do not display ecologically relevant physiologies such as the ability to form biofilms. Here we present a method that allows genetic transformation by natural competence in several environmental isolates of B. subtilis. Competence in these strains was established by expressing the B. subtilis competence transcription factor ComK from an IPTG-inducible promoter construct present on an unstable plasmid. This transiently activates expression of the genes required for DNA uptake and recombination in the host strain. After transformation, the comK encoding plasmid is lost easily because of its intrinsic instability and the transformed strain returns to its wild state. Using this method, we have successfully generated mutants and introduced foreign DNA into a number of environmental isolates and also B. subtilis strain NCIB3610, which is widely used to study biofilm formation. Application of the same method to strains of B. licheniformis was unsuccessful. The efficient and rapid approach described here may facilitate genetic studies in a wider array of environmental B. subtilis strains.

| S-EPMC2838798 | biostudies-literature

Structural characterization of the late competence protein ComFB from Bacillus subtilis.

Project description:Many bacteria take up DNA from their environment as part of the process of natural transformation. DNA uptake allows microorganisms to gain genetic diversity and can lead to the spread of antibiotic resistance or virulence genes within a microbial population. Development of genetic competence (Com) in Bacillus subtilis is a highly regulated process that culminates in expression of several late competence genes and formation of the DNA uptake apparatus. The late competence operon comF encodes a small protein of unknown function, ComFB. To gain insight into the function of ComFB, we determined its 3D structure via X-ray crystallography. ComFB is a dimer and each subunit consists of four ?-helices connected by short loops and one extended ?-strand-like stretch. Each subunit contains one zinc-binding site formed by four cysteines, which are unusually spaced in the primary sequence. Using structure- and bioinformatics-guided substitutions we analyzed the inter-subunit interface of the ComFB dimer. Based on these analyses, we conclude that ComFB is an obligate dimer. We also characterized ComFB in vivo and found that this protein is produced in competent cells and is localized to the cytosol. Consistent with previous reports, we showed that deletion of ComFB does not affect DNA uptake function. Combining our results, we conclude that ComFB is unlikely to be a part of the DNA uptake machinery under tested conditions and instead may have a regulatory function.

| S-EPMC4381287 | biostudies-literature

Noise Expands the Response Range of the Bacillus subtilis Competence Circuit.

Project description:Gene regulatory circuits must contend with intrinsic noise that arises due to finite numbers of proteins. While some circuits act to reduce this noise, others appear to exploit it. A striking example is the competence circuit in Bacillus subtilis, which exhibits much larger noise in the duration of its competence events than a synthetically constructed analog that performs the same function. Here, using stochastic modeling and fluorescence microscopy, we show that this larger noise allows cells to exit terminal phenotypic states, which expands the range of stress levels to which cells are responsive and leads to phenotypic heterogeneity at the population level. This is an important example of how noise confers a functional benefit in a genetic decision-making circuit.

| S-EPMC4803322 | biostudies-literature

Deciding fate in adverse times: sporulation and competence in Bacillus subtilis.

Project description:Bacteria serve as the central arena for understanding how gene networks and proteins process information and control cellular behaviors. Recently, much effort has been devoted to the investigation of specific bacteria gene circuits as functioning modules. The next challenge is the integrative modeling of complex cellular networks composed of many such modules. A tractable integrative model of the sophisticated decision-making signal transduction system that determines the fate between sporulation and competence is presented. This model provides an understanding of how information is sensed and processed to reach an "informative" decision in the context of cell state and signals from other cells. The competence module (ComK dynamics) is modeled as a stochastic switch whose transition rate is controlled by a quorum-sensing unit. The sporulation module (Spo0A dynamics) is modeled as a timer whose clock rate is adjusted by a stress-sensing unit. The interplay between these modules is mediated via the Rap assessment system, which gates the sensing units, and the AbrB-Rok decision module, which creates an opportunity for competence within a specific window of the sporulation timer. The timer is regulated via a special repressilator-like inhibition of Spo0A* by Spo0E, which is itself inhibited by AbrB. For some stress and input signals, this repressilator can generate a frustration state with large variations (fluctuations or oscillations) in Spo0A* and AbrB concentrations, which might serve an important role in generating cell variability. This integrative framework is a starting point that can be extended to include transition into cannibalism and the role of colony organization.

| S-EPMC2795487 | biostudies-literature

Studies on the competence-inducing factor of Bacillus subtilis.

Project description:1. Aqueous extracts of competent cells of Bacillus subtilis 168I(-) were shown to contain a competence-inducing factor. The aqueous extracts were fractionated on DEAE-cellulose columns. 2. Those fractions from DEAE-cellulose columns containing the competence-inducing factor were shown to exhibit a powerful lytic effect on isolated cell walls of B. subtilis 168I(-). Little or no lytic activity was exhibited by the other fractions. 3. The kinetics of the lytic enzyme were investigated and found to be first-order. Treatment of cell wall lysates with 1-fluoro-2,4-dinitrobenzene suggested that the enzyme may be identical with N-acetylmuramyl-l-alanine amidase. The amino acid composition of the partially purified enzyme was determined. 4. It is suggested that competence-induction may be dependent on the limited action of the autolytic amidase.

| S-EPMC1178873 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data