763 research outputs found
Directional persistence & the optimality of run-and-tumble chemotaxis
E. coli does chemotaxis by performing a biased random walk composed of alternating periods of swimming (runs) and reorientations (tumbles). Tumbles are typically modelled as complete directional randomisations but it is known that in wild type E. coli, successive run directions are actually weakly correlated, with a mean directional difference of not, vert, similar63°. We recently presented a model of the evolution of chemotactic swimming strategies in bacteria which is able to quantitatively reproduce the emergence of this correlation. The agreement between model and experiments suggests that directional persistence may serve some function, a hypothesis supported by the results of an earlier model. Here we investigate the effect of persistence on chemotactic efficiency, using a spatial Monte Carlo model of bacterial swimming in a gradient, combined with simulations of natural selection based on chemotactic efficiency. A direct search of the parameter space reveals two attractant gradient regimes, (a) a low-gradient regime, in which efficiency is unaffected by directional persistence and (b) a high-gradient regime, in which persistence can improve chemotactic efficiency. The value of the persistence parameter that maximises this effect corresponds very closely with the value observed experimentally. This result is matched by independent simulations of the evolution of directional memory in a population of model bacteria, which also predict the emergence of persistence in high-gradient conditions. The relationship between optimality and persistence in different environments may reflect a universal property of random-walk foraging algorithms, which must strike a compromise between two competing aims: exploration and exploitation. We also present a new graphical way to generally illustrate the evolution of a particular trait in a population, in terms of variations in an evolvable parameter
Resolving the binding-kinase discrepancy in bacterial chemotaxis: A nonequilibrium allosteric model and the role of energy dissipation
The Escherichia coli chemotaxis signaling pathway has served as a model
system for studying the adaptive sensing of environmental signals by large
protein complexes. The chemoreceptors control the kinase activity of CheA in
response to the extracellular ligand concentration and adapt across a wide
concentration range by undergoing methylation and demethylation. Methylation
shifts the kinase response curve by orders of magnitude in ligand concentration
while incurring a much smaller change in the ligand binding curve. Here, we
show that this asymmetric shift in binding and kinase response is inconsistent
with equilibrium allosteric models regardless of parameter choices. To resolve
this inconsistency, we present a nonequilibrium allosteric model that
explicitly includes the dissipative reaction cycles driven by ATP hydrolysis.
The model successfully explains all existing measurements for both aspartate
and serine receptors. Our results suggest that while ligand binding controls
the equilibrium balance between the ON and OFF states of the kinase, receptor
methylation modulates the kinetic properties (e.g., the phosphorylation rate)
of the ON state. Furthermore, sufficient energy dissipation is necessary for
maintaining and enhancing the sensitivity range and amplitude of the kinase
response. We demonstrate that the nonequilibrium allosteric model is broadly
applicable to other sensor-kinase systems by successfully fitting previously
unexplained data from the DosP bacterial oxygen-sensing system. Overall, this
work provides a new perspective on cooperative sensing by large protein
complexes and opens up new research directions for understanding their
microscopic mechanisms through simultaneous measurements and modeling of ligand
binding and downstream responses.Comment: 12 (main text) + 4 (supplemental information) pages, 6+4 figure
Adaptive response and enlargement of dynamic range
Many membrane channels and receptors exhibit adaptive, or desensitized,
response to a strong sustained input stimulus, often supported by protein
activity-dependent inactivation. Adaptive response is thought to be related to
various cellular functions such as homeostasis and enlargement of dynamic range
by background compensation. Here we study the quantitative relation between
adaptive response and background compensation within a modeling framework. We
show that any particular type of adaptive response is neither sufficient nor
necessary for adaptive enlargement of dynamic range. In particular a precise
adaptive response, where system activity is maintained at a constant level at
steady state, does not ensure a large dynamic range neither in input signal nor
in system output. A general mechanism for input dynamic range enlargement can
come about from the activity-dependent modulation of protein responsiveness by
multiple biochemical modification, regardless of the type of adaptive response
it induces. Therefore hierarchical biochemical processes such as methylation
and phosphorylation are natural candidates to induce this property in signaling
systems.Comment: Corrected typos, minor text revision
A Minimal Model of Metabolism Based Chemotaxis
Since the pioneering work by Julius Adler in the 1960's, bacterial chemotaxis has been predominantly studied as metabolism-independent. All available simulation models of bacterial chemotaxis endorse this assumption. Recent studies have shown, however, that many metabolism-dependent chemotactic patterns occur in bacteria. We hereby present the simplest artificial protocell model capable of performing metabolism-based chemotaxis. The model serves as a proof of concept to show how even the simplest metabolism can sustain chemotactic patterns of varying sophistication. It also reproduces a set of phenomena that have recently attracted attention on bacterial chemotaxis and provides insights about alternative mechanisms that could instantiate them. We conclude that relaxing the metabolism-independent assumption provides important theoretical advances, forces us to rethink some established pre-conceptions and may help us better understand unexplored and poorly understood aspects of bacterial chemotaxis
Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis
Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials
BINDING PROTEINS AND MEMBRANE TRANSPORT fn1
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72841/1/j.1749-6632.1975.tb31496.x.pd
Cyclic di-GMP differentially tunes a bacterial flagellar motor through a novel class of CheY-like regulators
The flagellar motor is a sophisticated rotary machine facilitating locomotion and signal transduction. Owing to its important role in bacterial behavior, its assembly and activity are tightly regulated. For example, chemotaxis relies on a sensory pathway coupling chemical information to rotational bias of the motor through phosphorylation of the motor switch protein CheY. Using a chemical proteomics approach, we identified a novel family of CheY-like (Cle) proteins in Caulobacter crescentus, which tune flagellar activity in response to binding of the second messenger c-di-GMP to a C-terminal extension. In their c-di-GMP bound conformation Cle proteins interact with the flagellar switch to control motor activity. We show that individual Cle proteins have adopted discrete cellular functions by interfering with chemotaxis and by promoting rapid surface attachment of motile cells. This study broadens the regulatory versatility of bacterial motors and unfolds mechanisms that tie motor activity to mechanical cues and bacterial surface adaptation
Chemoperception of Specific Amino Acids Controls Phytopathogenicity in Pseudomonas syringae pv. tomato
IMPORTANCE There is substantive evidence that chemotaxis is a key requisite for
efficient pathogenesis in plant pathogens. However, information regarding particular
bacterial chemoreceptors and the specific plant signal that they sense is scarce. Our
work shows that the phytopathogenic bacterium Pseudomonas syringae pv. tomato
mediates not only chemotaxis but also the control of pathogenicity through the perception
of the plant abundant amino acids Asp and Glu. We describe the specificity
of the perception of L- and D-Asp and L-Glu by the PsPto-PscA chemoreceptor and
the involvement of this perception in the regulation of pathogenicity-related traits.
Moreover, a saturating concentration of D-Asp reduces bacterial virulence, and we
therefore propose that ligand-mediated interference of key chemoreceptors may be
an alternative strategy to control virulence.Supplemental material for this article may be found at https://doi.org/10.1128/mBio
.01868-19.We acknowledge M. Trini Gallegos for kindly provide plasmid pCdrA::gfpS and S.
Nebreda for technical assistance.Chemotaxis has been associated with the pathogenicity of bacteria in
plants and was found to facilitate bacterial entry through stomata and wounds.
However, knowledge regarding the plant signals involved in this process is scarce.
We have addressed this issue using Pseudomonas syringae pv. tomato, which is a foliar
pathogen that causes bacterial speck in tomato. We show that the chemoreceptor
P. syringae pv. tomato PscA (PsPto-PscA) recognizes specifically and with high affinity
L-Asp, L-Glu, and D-Asp. The mutation of the chemoreceptor gene largely
reduced chemotaxis to these ligands but also altered cyclic di-GMP (c-di-GMP) levels,
biofilm formation, and motility, pointing to cross talk between different chemosensory
pathways. Furthermore, the PsPto-PscA mutant strain showed reduced virulence
in tomato. Asp and Glu are the most abundant amino acids in plants and in particular
in tomato apoplasts, and we hypothesize that this receptor may have evolved to
specifically recognize these compounds to facilitate bacterial entry into the plant. Infection
assays with the wild-type strain showed that the presence of saturating concentrations
of D-Asp also reduced bacterial virulence.This work was supported by grants AGL2015-63851-R and RTI2018-095222-B100 (to
E.L.-S.) and BIO2016-76779-P (to T.K.) from the Ministerio de Economía y Competitividad,
Spain. J.P.C.-V. was supported by the FPI program (BES-2016-076452, MINECOSpain)
Two Component Systems: Physiological Effect of a Third Component
Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS). These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK) and by a response regulator (RR) that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call “third component”) on the functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible
Self-Organization of the Escherichia coli Chemotaxis Network Imaged with Super-Resolution Light Microscopy
Photoactivated localization microscopy analysis of chemotaxis receptors in bacteria suggests that the non-random organization of these proteins results from random self-assembly of clusters without direct cytoskeletal involvement or active transport
- …