Kegg Pathway: Bacterial chemotaxis - General

J Proteome Res. 2009 Jan; 8(1): 59-71
Chourey K, Thompson MR, Shah M, Zhang B, Verberkmoes NC, Thompson DK, Hettich RL

Predicted orphan response regulators encoded in the Shewanella oneidensis MR-1 genome are poorly understood from a cellular function perspective. Our previous transcriptomic and proteomic analyses demonstrated that an annotated DNA-binding response regulator, SO2426, was significantly up-regulated in wild-type S. oneidensis cells at both the mRNA and protein levels in response to acute chromate [Cr(VI)] challenge, suggesting a potential regulatory role for this protein in metal stress pathways. To investigate the impact of SO2426 activity on chromate stress response at a genome-wide scale, we describe here comparative and temporal proteome characterizations using multidimensional HPLC-MS/MS and statistical analysis to identify differentially expressed proteins in biological replicates of wild-type S. oneidensis MR-1 and a so2426 deletion (Deltaso2426) strain, which exhibited an impaired Cr(VI) transformation rate compared to that of the parental strain. Global protein profiles were examined at different time intervals (0, 1, 3, 4 h) following exogenous chromate challenge. Results indicated that deletion of the so2426 gene negatively affected expression of a small protein subset (27 proteins) including those with annotated functions in siderophore biosynthesis (SO3032), Fe uptake (SO4743), intracellular Fe storage (Bfr1), and other transport processes. Cr(VI) exposure and subsequent transformation dramatically increased the number of differentially expressed proteins detected, with up-regulated abundance patterns observed largely for proteins involved in General stress protection and detoxification strategies, cell motility, and protein fate. In addition, the proteome data sets were mined for amino acids with potential post-translational modifications (PTMs) indicative of a level of gene expression regulation extending beyond the transcriptional control imposed by SO2426.

J Phys Chem B. 2008 Dec 2;
Drengstig T, Ueda HR, Ruoff P

Adaptation and compensation mechanisms are important to keep organisms fit in a changing environment. "Perfect adaptation" describes an organism's response to an external stepwise perturbation by resetting some of its variables precisely to their original preperturbation values. Examples of perfect adaptation are found in Bacterial chemotaxis, photoreceptor responses, or MAP kinase activities. Two concepts have evolved for how perfect adaptation may be understood. In one approach, so-called "robust perfect adaptation", the adaptation is a network property (due to integral feedback control), which is independent of rate constant values. In the other approach, which we have termed "nonrobust perfect adaptation", a fine-tuning of rate constant values is needed to show perfect adaptation. Although integral feedback describes robust perfect adaptation in General terms, it does not directly show where in a network perfect adaptation may be observed. Using control theoretic methods, we are able to predict robust perfect adaptation sites within reaction kinetic networks and show that a prerequisite for robust perfect adaptation is that the network is open and irreversible. We applied the method on various reaction schemes and found that new (robust) perfect adaptation motifs emerge when considering suggested models of Bacterial and eukaryotic chemotaxis.

Lab Chip. 2008 Dec; 8(12): 2054-61
Agrawal N, Toner M, Irimia D

Neutrophil directional migration in response to chemical gradients, also known as chemotaxis, is one of the key phenomena in the immune responses against Bacterial infection. To better study neutrophils chemotaxis, several in vitro assays have been developed that replicate chemotactic gradients around neutrophils isolated from whole blood. One drawback for most of these assays is the lengthy processing of blood required for neutrophils isolation, which can alter the responsiveness of neutrophils compared to the in vivo conditions. To address this limitation, we have designed a microfluidic chip for chemotaxis studies which can use neutrophils isolated on the chip, directly from whole blood. We have tested three different cell adhesion molecules as substrates for neutrophil isolation (P-selectin, E-selectin and fibronectin) and found average capture efficiencies of 20-40 neutrophils/mm2 at optimized concentrations. Subsequent analysis of neutrophil migration in chemoattractant gradients of N-formyl-methyl-leucyl-phenylalanine (fMLP) or Interleukin-8 (IL-8) shows higher average velocities over E-selectin as compared to the P-selectin. Our microfluidic assay uses just a drop of whole blood (<10 microL) for neutrophil isolation and provides a robust platform to perform chemotaxis assays in the competing environment of different chemokines.

J Infect Dis. 2008 Dec 15; 198(12): 1851-5
Cosma CL, Humbert O, Sherman DR, Ramakrishnan L

Although tuberculous granulomas, which are composed of infected macrophages and other immune cells, have long been considered impermeable structures, recent studies have shown that superinfecting Mycobacterium marinum traffic rapidly to established fish and frog granulomas by host-mediated and Mycobacterium-directed mechanisms. The present study shows that superinfecting Mycobacterium tuberculosis and Mycobacterium bovis bacille Calmette-Guérin similarly home to established granulomas in mice. Furthermore, 2 prominent mycoBacterial virulence determinants, Erp and ESX-1, do not affect this cellular trafficking. These findings suggest that homing of infected macrophages to sites of infection is a General feature of the pathogenesis of tuberculosis and has important consequences for therapeutic strategies.

Proc Natl Acad Sci U S A. 2008 Sep 30; 105(39): 14855-60
Tu Y, Shimizu TS, Berg HC

In their natural environment, cells need to extract useful information from complex temporal signals that vary over a wide range of intensities and time scales. Here, we study how such signals are processed by Escherichia coli during chemotaxis by developing a General theoretical model based on receptor adaptation and receptor-receptor cooperativity. Measured responses to various monotonic, oscillatory, and impulsive stimuli are all explained consistently by the underlying adaptation kinetics within this model. For exponential ramp signals, an analytical solution is discovered that reveals a remarkable connection between the dependence of kinase activity on the exponential ramp rate and the receptor methylation rate function. For exponentiated sine-wave signals, spectral analysis shows that the chemotaxis pathway acts as a lowpass filter for the derivative of the signal with the cutoff frequency determined by an intrinsic adaptation time scale. For large step stimuli, we find that the recovery time is determined by the constant maximum methylation rate, which provides a natural explanation for the observed recovery time additivity. Our model provides a quantitative system-level description of the chemotaxis signaling pathway and can be used to predict E. coli chemotaxis responses to arbitrary temporal signals. This model of the receptor system reveals the molecular origin of Weber's law in Bacterial chemotaxis. We further identify additional constraints required to account for the related observation that the output of this pathway is constant under exponential ramp stimuli, a feature that we call "logarithmic tracking."

Appl Environ Microbiol. 2008 Nov; 74(22): 7002-15
Lemuth K, Hardiman T, Winter S, Pfeiffer D, Keller MA, Lange S, Reuss M, Schmid RD, Siemann-Herzberg M

A time series of whole-genome transcription profiling of Escherichia coli K-12 W3110 was performed during a carbon-limited fed-batch process. The application of a constant feed rate led to the identification of a dynamic sequence of diverse carbon limitation responses (e.g., the hunger response) and at the same time provided a global view of how cellular and extracellular resources are used: the synthesis of high-affinity transporters guarantees maximal glucose influx, thereby preserving the phosphoenolpyruvate pool, and energy-dependent chemotaxis is reduced in order to provide a more economic "work mode." sigma(S)-mediated stress and starvation responses were both found to be of only minor relevance. Thus, the experimental setup provided access to the hunger response and enabled the differentiation of the hunger response from the General starvation response. Our previous topological model of the global regulation of the E. coli central carbon metabolism through the crp, cra, and relA/spoT modulons is supported by correlating transcript levels and metabolic fluxes and can now be extended. The substrate is extensively oxidized in the tricarboxylic acid (TCA) cycle to enhance energy generation. However, the General rate of oxidative decarboxylation within the pentose phosphate pathway and the TCA cycle is restricted to a minimum. Fine regulation of the carbon flux through these pathways supplies sufficient precursors for biosyntheses. The pools of at least three precursors are probably regulated through activation of the (phosphoenolpyruvate-)glyoxylate shunt. The present work shows that detailed understanding of the genetic regulation of Bacterial metabolism provides useful insights for manipulating the carbon flux in technical production processes.

Proc Natl Acad Sci U S A. 2008 Aug 26; 105(34): 12289-94
Besschetnova TY, Montefusco DJ, Asinas AE, Shrout AL, Antommattei FM, Weis RM

All cells possess transmembrane signaling systems that function in the environment of the lipid bilayer. In the Escherichia coli chemotaxis pathway, the binding of attractants to a two-dimensional array of receptors and signaling proteins simultaneously inhibits an associated kinase and stimulates receptor methylation--a slower process that restores kinase activity. These two opposing effects lead to robust adaptation toward stimuli through a physical mechanism that is not understood. Here, we provide evidence of a counterbalancing influence exerted by receptor density on kinase stimulation and receptor methylation. Receptor signaling complexes were reconstituted over a range of defined surface concentrations by using a template-directed assembly method, and the kinase and receptor methylation activities were measured. Kinase activity and methylation rates were both found to vary significantly with surface concentration--yet in opposite ways: samples prepared at high surface densities stimulated kinase activity more effectively than low-density samples, whereas lower surface densities produced greater methylation rates than higher densities. FRET experiments demonstrated that the cooperative change in kinase activity coincided with a change in the arrangement of the membrane-associated receptor domains. The counterbalancing influence of density on receptor methylation and kinase stimulation leads naturally to a model for signal regulation that is compatible with the known logic of the E. coli pathway. Density-dependent mechanisms are likely to be General and may operate when two or more membrane-related processes are influenced differently by the two-dimensional concentration of pathway elements.

J Mol Biol. 2008 Oct 3; 382(2): 485-95
Hills RD, Brooks CL

The folding of multidomain proteins often proceeds in a hierarchical fashion with individual domains folding independent of one another. A large single-domain protein, however, can consist of multiple modules whose folding may be autonomous or interdependent in ways that are unclear. We used coarse-grained simulations to explore the folding landscape of the two-subdomain Bacterial response regulator CheY. Thermodynamic and kinetic characterization shows the landscape to be highly analogous to the four-state landscape reported for another two-subdomain protein, T4 lysozyme. An on-pathway intermediate structured in the more stable nucleating subdomain was observed, as were transient states frustrated in off-pathway contacts prematurely structured in the weaker subdomain. Local unfolding, or backtracking, was observed in the frustrated state before the native conformation could be reached. Nonproductive frustration was attributable to competition for van der Waals contacts between the two subdomains. In an accompanying article, stopped-flow kinetic measurements support an off-pathway burst-phase intermediate, seemingly consistent with our prediction of early frustration in the folding landscape of CheY. Comparison of the folding mechanisms for CheY, T4 lysozyme, and interleukin-1 beta leads us to postulate that subdomain competition is a General feature of large single-domain proteins with multiple folding modules.

Biosystems. 2008 Oct-Nov; 94(1-2): 47-54
Nicolau DV, Burrage K, Nicolau DV, Maini PK

We present a General-purpose optimization algorithm inspired by "run-and-tumble", the biased random walk chemotactic swimming strategy used by the bacterium Escherichia coli to locate regions of high nutrient concentration The method uses particles (corresponding to bacteria) that swim through the variable space (corresponding to the attractant concentration profile). By constantly performing temporal comparisons, the particles drift towards the minimum or maximum of the function of interest. We illustrate the use of our method with four examples. We also present a discrete version of the algorithm. The new algorithm is expected to be useful in combinatorial optimization problems involving many variables, where the functional landscape is apparently stochastic and has local minima, but preserves some derivative structure at intermediate scales.

Microbiology. 2008 Feb; 154(Pt 2): 462-75
Bowman JP, Bittencourt CR, Ross T

High hydrostatic pressure processing (HPP) is currently being used as a treatment for certain foods to control the presence of food-borne pathogens, such as Listeria monocytogenes. Genomic microarray analysis was performed to determine the effects of HPP on L. monocytogenes in order to understand how it responds to mechanical stress injury. Reverse transcriptase PCR analysis of tufA and rpoC indicated that the reduction of mRNA expression in HPP-treated cells was dependent on intensity and time of the treatment. Treatments of 400 and 600 MPa for 5 min on cells in the exponential growth phase, though leading to partial or complete cellular inactivation, still resulted in measurable relative differential gene expression. Gene set enrichment analysis indicated that HPP induced increased expression of genes associated with DNA repair mechanisms, transcription and translation protein complexes, the septal ring, the General protein translocase system, flagella assemblage and chemotaxis, and lipid and peptidoglycan biosynthetic pathways. On the other hand, HPP appears to suppress a wide range of energy production and conversion, carbohydrate metabolism and virulence-associated genes accompanied by strong suppression of the SigB and PrfA regulons. HPP also affected genes controlled by the pleotrophic regulator CodY. HPP-induced cellular damage appears to lead to increased expression of genes linked to sections of the cell previously shown in bacteria to be damaged or altered during HPP exposure and suppression of gene expression associated with cellular growth processes and virulence.

Curr Diabetes Rev. 2005 Aug; 1(3): 343-7
Ojetti V, Migneco A, Silveri NG, Ghirlanda G, Gasbarrini G, Gasbarrini A

Helicobacter pylori [H. pylori], one of the most common chronic infections worldwide, is the main etiologic agent of gastritis, peptic ulcer and gastric cancer. Patients with diabetes mellitus are often affected by chronic infections. Many studies have evaluated the prevalence of H. pylori infection in diabetic patients and the possible role of this condition in their metabolic control. Some studies found a higher prevalence of the infection in diabetic patients and a reduced glycaemic control, while others did not support any correlation between metabolic control and H. pylori infection. There are only a few studies on the eradication rate of H. pylori in diabetic patients. Most of these papers concluded that standard antibiotic therapy allows a significantly lower H. pylori eradication rate than is observed in control groups matched for sex and age. Changes in the microvasculature of the stomach with a possible reduction of antibiotic absorption, the presence of gastroparesis and the frequent use of antibiotics for recurrent Bacterial infections with the development of resistant strains could be some of the mechanisms underlying this phenomenon. A quadruple therapy may be used as the second line approach with a good eradication rate, even if an antibiotic selected according to a specific H. pylori antibiogram is considered the gold standard in these patients. As regards the gastrointestinal symptoms of H. pylori infected individuals, many studies showed that they are as frequent in patients with type 1 diabetes as in the General population. The incidence of H. pylori recurrence after 12 months follow-up is significantly higher in type 1 diabetic subjects when compared to controls. Reduced lymphocyte activity, neutrophil dysfunction with failure of chemotaxis and a possible reservoir of H. pylori in dental plaque may explain the higher rate of re-infection in these patients.