Comparative analysis of two paradigm bacteriophytochromes reveals opposite functionalities in two-component signaling.
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ABSTRACT:
SUBMITTER: Multamaki E
PROVIDER: S-EPMC8292422 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
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Project description:Pseudomonas syringae is a widespread bacterial plant pathogen, and strains of P. syringae may be assigned to different pathovars based on host specificity among different plant species. The genomes of P. syringae pv. syringae (Psy) B728a, pv. tomato (Pto) DC3000 and pv. phaseolicola (Pph) 1448A have been recently sequenced providing a major resource for comparative genomic analysis. A mechanism commonly found in bacteria for signal transduction is the two-component system (TCS), which typically consists of a sensor histidine kinase (HK) and a response regulator (RR). P. syringae requires a complex array of TCS proteins to cope with diverse plant hosts, host responses, and environmental conditions.Based on the genomic data, pattern searches with Hidden Markov Model (HMM) profiles have been used to identify putative HKs and RRs. The genomes of Psy B728a, Pto DC3000 and Pph 1448A were found to contain a large number of genes encoding TCS proteins, and a core of complete TCS proteins were shared between these genomes: 30 putative TCS clusters, 11 orphan HKs, 33 orphan RRs, and 16 hybrid HKs. A close analysis of the distribution of genes encoding TCS proteins revealed important differences in TCS proteins among the three P. syringae pathovars.In this article we present a thorough analysis of the identification and distribution of TCS proteins among the sequenced genomes of P. syringae. We have identified differences in TCS proteins among the three P. syringae pathovars that may contribute to their diverse host ranges and association with plant hosts. The identification and analysis of the repertoire of TCS proteins in the genomes of P. syringae pathovars constitute a basis for future functional genomic studies of the signal transduction pathways in this important bacterial phytopathogen.
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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