Different evolutionary modifications as a guide to rewire two-component systems.
Ontology highlight
ABSTRACT:
SUBMITTER: Krueger B
PROVIDER: S-EPMC3348925 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Different evolutionary modifications as a guide to rewire two-component systems.
Krueger Beate B Friedrich Torben T Förster Frank F Bernhardt Jörg J Gross Roy R Dandekar Thomas T
Bioinformatics and biology insights 20120503
Two-component systems (TCS) are short signalling pathways generally occurring in prokaryotes. They frequently regulate prokaryotic stimulus responses and thus are also of interest for engineering in biotechnology and synthetic biology. The aim of this study is to better understand and describe rewiring of TCS while investigating different evolutionary scenarios. Based on large-scale screens of TCS in different organisms, this study gives detailed data, concrete alignments, and structure analysis ...[more]
Similar Datasets
Project description:The prevalent paradigm governing bacterial two-component signaling systems (TCSs) is specificity, wherein the histidine kinase (HK) of a TCS exclusively activates its cognate response regulator (RR). Cross talk, where HKs activate noncognate RRs, is considered evolutionarily disadvantageous because it can compromise adaptive responses by leaking signals. Yet cross talk is observed in several bacteria. Here, to resolve this paradox, we propose an alternative paradigm where cross talk can be advantageous. We envisioned programmed environments, wherein signals appear in predefined sequences. In such environments, cross talk that primes bacteria to upcoming signals may improve adaptive responses and confer evolutionary benefits. To test this hypothesis, we employed mathematical modeling of TCS signaling networks and stochastic evolutionary dynamics simulations. We considered the comprehensive set of bacterial phenotypes, comprising thousands of distinct cross talk patterns competing in varied signaling environments. Our simulations predicted that in programmed environments phenotypes with cross talk facilitating priming would outcompete phenotypes without cross talk. In environments where signals appear randomly, bacteria without cross talk would dominate, explaining the specificity widely seen. Additionally, a testable prediction was that the phenotypes selected in programmed environments would display one-way cross talk, ensuring priming to future signals. Interestingly, the cross talk networks we deduced from available data on TCSs of Mycobacterium tuberculosis all displayed one-way cross talk, which was consistent with our predictions. Our study thus identifies potential evolutionary underpinnings of cross talk in bacterial TCSs, suggests a reconciliation of specificity and cross talk, makes testable predictions of the nature of cross talk patterns selected, and has implications for understanding bacterial adaptation and the response to interventions. IMPORTANCE Bacteria use two-component signaling systems (TCSs) to sense and respond to environmental changes. The prevalent paradigm governing TCSs is specificity, where signal flow through TCSs is insulated; leakage to other TCSs is considered evolutionarily disadvantageous. Yet cross talk between TCSs is observed in many bacteria. Here, we present a potential resolution of this paradox. We envision programmed environments, wherein stimuli appear in predefined sequences. Cross talk that primes bacteria to upcoming stimuli could then confer evolutionary benefits. We demonstrate this benefit using mathematical modeling and evolutionary simulations. Interestingly, we found signatures of predicted cross talk patterns in Mycobacterium tuberculosis. Furthermore, specificity was selected in environments where stimuli occurred randomly, thus reconciling specificity and cross talk. Implications follow for understanding bacterial evolution and for interventions.
| S-EPMC9765234 | biostudies-literature
Project description:To analyze function of three Two-component systems SAOUHSC_00184-185, SAOUHSC_01313-1314, and SAOUHSC_01980-1981, we have employed whole genome microarray expression profiling to identify genes transcription changed in respective mutant strains. Target TCSs were replaced by ermB gene.
2013-09-30 | GSE51197 | GEO
Project description:To analyze function of three Two-component systems SAOUHSC_00184-185, SAOUHSC_01313-1314, and SAOUHSC_01980-1981, we have employed whole genome microarray expression profiling to identify genes transcription changed in respective mutant strains. Target TCSs were replaced by ermB gene. Cells were grown to OD600=2.0, and the RNA level of wild type NCTC8325 and three TCSs mutant were compared.
2013-09-30 | E-GEOD-51197 | biostudies-arrayexpress
Project description:Two-component signal transduction pathways are one of the primary means by which microorganisms respond to environmental signals. These signaling cascades originated in prokaryotes and were inherited by eukaryotes via endosymbiotic lateral gene transfer from ancestral cyanobacteria. We report here that the nuclear genome of pathogenic fungus Candida albicans contains elements of a two-component signaling pathway that seem to be targeted to the mitochondria. In C. albicans two-component response regulator protein Srr1(Stress Response Regulator) contains a mitochondrial targeting sequence at the N-terminus, and fluorescence microscopy reveals mitochondrial localization of GFP-tagged Srr1p. Moreover, phylogenetic analysis indicates that C. albicans Srr1p is more closely related to histidine kinases and response regulators found in marine bacteria compared to other two-component proteins present in the fungi. These data suggest conservation of this protein during the evolutionary transition from endosymbiont to a subcellular organelle. We used microarray analysis to determine if the phenotypes observed with srr1Δ/Δ mutant could be correlated with gene transcriptional changes. Expression of mitochondrial genes was altered in the srr1Δ/Δ null mutant in comparison to the wild type. Furthermore, apoptosis significantly increased in the srr1Δ/Δ mutant strain compared to wild type, suggesting activation of mitochondria dependent apoptotic cell death pathway in the srr1Δ/Δ mutant. This study shows for the first time that a lower eukaryote like C. albicans possesses a two-component response regulator protein that has survived in mitochondria and regulates a subset of genes whose functions are associated with oxidative stress response and programmed cell death (apoptosis).
2013-07-02 | GSE45438 | GEO
Project description:Two-component systems including histidine protein kinases represent the primary signal transduction paradigm in prokaryotic organisms. To understand how these systems adapt to allow organisms to detect niche-specific signals, we analyzed the phylogenetic distribution of nearly 5,000 histidine protein kinases from 207 sequenced prokaryotic genomes. We found that many genomes carry a large repertoire of recently evolved signaling genes, which may reflect selective pressure to adapt to new environmental conditions. Both lineage-specific gene family expansion and horizontal gene transfer play major roles in the introduction of new histidine kinases into genomes; however, there are differences in how these two evolutionary forces act. Genes imported via horizontal transfer are more likely to retain their original functionality as inferred from a similar complement of signaling domains, while gene family expansion accompanied by domain shuffling appears to be a major source of novel genetic diversity. Family expansion is the dominant source of new histidine kinase genes in the genomes most enriched in signaling proteins, and detailed analysis reveals that divergence in domain structure and changes in expression patterns are hallmarks of recent expansions. Finally, while these two modes of gene acquisition are widespread across bacterial taxa, there are clear species-specific preferences for which mode is used.
| S-EPMC1630713 | biostudies-literature
Project description: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.
| S-EPMC3281920 | biostudies-literature
Project description:Bacteria alter gene expression in response to changes in their environment through various mechanisms that include signal transduction systems. These signal transduction systems use membrane histidine kinase with sensing domains to mediate phosphotransfer to DNA-binding proteins that alter the level of gene expression. Such regulators are called two-component systems (TCSs). TCSs integrate external signals and information from stress pathways, central metabolism and other global regulators, thus playing an important role as part of the overall regulatory network. This review will focus on the knowledge of TCSs in the Gram-negative bacterium, Francisella tularensis, a biothreat agent with a wide range of potential hosts and a significant ability to cause disease. While TCSs have been well-studied in several bacterial pathogens, they have not been well-studied in non-model organisms, such as F. tularensis and its subspecies, whose canonical TCS content surprisingly ranges from few to none. Additionally, of those TCS genes present, many are orphan components, including KdpDE, QseC, QseB/PmrA, and an unnamed two-component system (FTN_1452/FTN_1453). We discuss recent advances in this field related to the role of TCSs in Francisella physiology and pathogenesis and compare the TCS genes present in human virulent versus. environmental species and subspecies of Francisella.
| S-EPMC6584805 | biostudies-literature
Project description:Two-component signal transduction pathways are one of the primary means by which microorganisms respond to environmental signals. These signaling cascades originated in prokaryotes and were inherited by eukaryotes via endosymbiotic lateral gene transfer from ancestral cyanobacteria. We report here that the nuclear genome of pathogenic fungus Candida albicans contains elements of a two-component signaling pathway that seem to be targeted to the mitochondria. In C. albicans two-component response regulator protein Srr1(Stress Response Regulator) contains a mitochondrial targeting sequence at the N-terminus, and fluorescence microscopy reveals mitochondrial localization of GFP-tagged Srr1p. Moreover, phylogenetic analysis indicates that C. albicans Srr1p is more closely related to histidine kinases and response regulators found in marine bacteria compared to other two-component proteins present in the fungi. These data suggest conservation of this protein during the evolutionary transition from endosymbiont to a subcellular organelle. We used microarray analysis to determine if the phenotypes observed with srr1M-NM-^T/M-NM-^T mutant could be correlated with gene transcriptional changes. Expression of mitochondrial genes was altered in the srr1M-NM-^T/M-NM-^T null mutant in comparison to the wild type. Furthermore, apoptosis significantly increased in the srr1M-NM-^T/M-NM-^T mutant strain compared to wild type, suggesting activation of mitochondria dependent apoptotic cell death pathway in the srr1M-NM-^T/M-NM-^T mutant. This study shows for the first time that a lower eukaryote like C. albicans possesses a two-component response regulator protein that has survived in mitochondria and regulates a subset of genes whose functions are associated with oxidative stress response and programmed cell death (apoptosis). Candida albicans wildtype or srr1 null cells were left untreated or were treated with either 8mM H2O2 for one hour prior to RNA isolation.
2013-07-02 | E-GEOD-45438 | biostudies-arrayexpress
Project description:Two component systems (TCS) are signal transduction pathways which typically consist of a sensor histidine kinase (HK) and a response regulator (RR). In this study, we have analyzed the evolution of TCS of the OmpR/IIIA family in Lactobacillaceae and Leuconostocaceae, two families belonging to the group of lactic acid bacteria (LAB). LAB colonize nutrient-rich environments such as foodstuffs, plant materials and the gastrointestinal tract of animals thus driving the study of this group of both basic and applied interest.The genomes of 19 strains belonging to 16 different species have been analyzed. The number of TCS encoded by the strains considered in this study varied between 4 in Lactobacillus helveticus and 17 in Lactobacillus casei. The OmpR/IIIA family was the most prevalent in Lactobacillaceae accounting for 71% of the TCS present in this group. The phylogenetic analysis shows that no new TCS of this family has recently evolved in these Lactobacillaceae by either lineage-specific gene expansion or domain shuffling. Furthermore, no clear evidence of non-orthologous replacements of either RR or HK partners has been obtained, thus indicating that coevolution of cognate RR and HKs has been prevalent in Lactobacillaceae.The results obtained suggest that vertical inheritance of TCS present in the last common ancestor and lineage-specific gene losses appear as the main evolutionary forces involved in their evolution in Lactobacillaceae, although some HGT events cannot be ruled out. This would agree with the genomic analyses of Lactobacillales which show that gene losses have been a major trend in the evolution of this group.
| S-EPMC3040137 | biostudies-literature
Project description:In the Staphylococcus aureus genome, a set of highly conserved two-component systems (TCSs) composed of histidine kinases (HKs) and their cognate response regulators (RRs) sense and respond to environmental stimuli, which drive the adaptation of the bacteria. This study investigates the complex interplay between TCSs in S. aureus USA300, a predominant methicillin-resistant S. aureus strain, revealing shared and unique virulence regulatory pathways and genetic variations mediating signal specificity within TCSs. Using TCS-related mutants from the Nebraska Transposon Mutant Library, we analyzed the effects of inactivated TCS HKs and RRs on the production of various virulence factors, in vitro infection abilities, and adhesion assays. We found that the TCSs' influence on virulence determinants was not associated with their phylogenetic relationship, indicating divergent functional evolution. Using the co-crystallized structure of the DesK-DesR from Bacillus subtilis and the modeled structures of the four NarL TCSs in S. aureus, we identified interacting residues, revealing specificity determinants and conservation within the same TCS, even from different strain backgrounds. The interacting residues were highly conserved within strains but varied between species due to selection pressures and the coevolution of cognate pairs. This study unveils the complex interplay and divergent functional evolution of TCSs, highlighting their potential for future experimental exploration of phosphotransfer between cognate and non-cognate recombinant HK and RRs.IMPORTANCEGiven the widespread conservation of two-component systems (TCSs) in bacteria and their pivotal role in regulating metabolic and virulence pathways, they present a compelling target for anti-microbial agents, especially in the face of rising multi-drug-resistant infections. Harnessing TCSs therapeutically necessitates a profound understanding of their evolutionary trajectory in signal transduction, as this underlies their unique or shared virulence regulatory pathways. Such insights are critical for effectively targeting TCS components, ensuring an optimized impact on bacterial virulence, and mitigating the risk of resistance emergence via the evolution of alternative pathways. Our research offers an in-depth exploration of virulence determinants controlled by TCSs in S. aureus, shedding light on the evolving specificity determinants that orchestrate interactions between their cognate pairs.
| S-EPMC11019936 | biostudies-literature