Identification of UvrY as the Cognate Response Regulator for the BarA Sensor Kinase in Escherichia coli

Pernestig, Anna-Karin; Melefors, Öjar; Georgellis, Dimitris

doi:10.1074/jbc.m001550200

Cited by 153 publications

(169 citation statements)

References 46 publications

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“…Interestingly, one of the SOS promoters, uvrY, is found to have a large error (Ϸ45%). This operon has been recently found to participate in a twocomponent signaling system related to stationary-phase response (27,28), and there is evidence that it is regulated by transcription factors other than LexA (29). The relatively large 30% error of polB may hint that it also has slight, as of yet uncharacterized, additional regulation.…”

Section: Detection Of Promoters With Additional Regulationmentioning

confidence: 99%

Assigning numbers to the arrows: Parameterizing a gene regulation network by using accurate expression kinetics

Ronen

Rosenberg

Shraiman

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

480

445

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A basic challenge in systems biology is to understand the dynamical behavior of gene regulation networks. Current approaches aim at determining the network structure based on genomic-scale data. However, the network connectivity alone is not sufficient to define its dynamics; one needs to also specify the kinetic parameters for the regulation reactions. Here, we ask whether effective kinetic parameters can be assigned to a transcriptional network based on expression data. We present a combined experimental and theoretical approach based on accurate high temporal-resolution measurement of promoter activities from living cells by using green fluorescent protein (GFP) reporter plasmids. We present algorithms that use these data to assign effective kinetic parameters within a mathematical model of the network. To demonstrate this, we employ a well defined network, the SOS DNA repair system of Escherichia coli. We find a strikingly detailed temporal program of expression that correlates with the functional role of the SOS genes and is driven by a hierarchy of effective kinetic parameter strengths for the various promoters. The calculated parameters can be used to determine the kinetics of all SOS genes given the expression profile of just one representative, allowing a significant reduction in complexity. The concentration profile of the master SOS transcriptional repressor can be calculated, demonstrating that relative protein levels may be determined from purely transcriptional data. This finding opens the possibility of assigning kinetic parameters to transcriptional networks on a genomic scale.T here is much interest in understanding the design principles underlying the structure and dynamics of gene regulation networks (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)36). Determining the dynamic behavior of these systems requires specifying not only the network connectivity, but also the kinetic parameters for the various regulation reactions. Standard biochemical methods of measuring these kinetic parameters are usually done outside of the cellular context and cannot be easily scaled up to a genomic level. It would therefore be valuable to develop methods to assign effective kinetic parameters to transcriptional networks based on in vivo measurements. Here we present an approach for determining the effective kinetic parameters of a transcriptional network based on accurate promoter activity measurements and analysis algorithms (Fig. 1).We developed a system for real-time monitoring of the transcriptional activity of operons by means of low-copy reporter plasmids (10) in which a promoter controls green fluorescent protein (GFP) (11). In each plasmid a different promoter controls the transcription rate of the same reporter gene, gfp, and thus rate of transcript production from the promoter is proportional to the rate of GFP accumulation. By continuous measurements from living cells grown in a multiwell plate fluorimeter, high-resolution time courses of the promoter strength and cell density are obtained. With this method, temporal...

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Section: Detection Of Promoters With Additional Regulationmentioning

confidence: 99%

Assigning numbers to the arrows: Parameterizing a gene regulation network by using accurate expression kinetics

Ronen

Rosenberg

Shraiman

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

480

445

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“…The BarA/UvrY two-component system (TCS) (also referred to as GacS/GacA, VarS/VarA, ExpS/ExpA, LetS/LetA, and BarA/SirA in various species) is the primary regulator of csrB and csrC expression and is highly conserved throughout the Gammaproteobacteria (Table 1) (58,66). BarA is a membrane-bound, tripartite histidine sensor kinase that uses an unusual phosphorelay mechanism to phosphorylate its cognate response regulator, UvrY (66). BarA activity is stimulated by short-chain fatty acids (SCFAs), the potency of which is negatively correlated with the aliphatic chain length (67,68).…”

Section: Regulation Of the Csr/rsm Systemmentioning

confidence: 99%

Regulation of Bacterial Virulence by Csr (Rsm) Systems

Vakulskas

Potts

Babitzke

et al. 2015

Microbiol Mol Biol Rev

302

400

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SUMMARY Most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. This ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. It is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. Studies over the past 2 decades have established that the CsrA/RsmA proteins, global regulators of posttranscriptional gene expression, play important roles in the expression of virulence factors of numerous proteobacterial pathogens. To accomplish these tasks, CsrA binds to the 5′ untranslated and/or early coding regions of mRNAs and alters translation, mRNA turnover, and/or transcript elongation. CsrA activity is regulated by noncoding small RNAs (sRNAs) that contain multiple CsrA binding sites, which permit them to sequester multiple CsrA homodimers away from mRNA targets. Environmental cues sensed by two-component signal transduction systems and other regulatory factors govern the expression of the CsrA-binding sRNAs and, ultimately, the effects of CsrA on secretion systems, surface molecules and biofilm formation, quorum sensing, motility, pigmentation, siderophore production, and phagocytic avoidance. This review presents the workings of the Csr system, the paradigm shift that it generated for understanding posttranscriptional regulation, and its roles in virulence networks of animal and plant pathogens.

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“…We tested all thirteen HKs that are partners of other PhoB family RRs for cross activation of PhoB. We also tested the HK BarA (the partner of the NarL family RR UvrY [Pernestig et al, 2001]) because BarA has been shown elsewhere to activate the PhoB family RR OmpR [Nagasawa et al, 1992]. Our search revealed four HKs (ArcB, CreC, KdpD, and QseC) that strongly activate PhoB, two HKs (BaeS and EnvZ) that weakly activate PhoB, and eight other HKs that failed to activate PhoB [Blackman et al, 2005].…”

Section: Effect Of L-rhamnose Concentration On Activationmentioning

confidence: 99%

Stochastic activation of the response regulator PhoB by noncognate histidine kinases

Zhou

Grégori

Blackman

et al. 2005

Journal of Integrative Bioinformatics

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Two-component systems (TCS) are the most prevalent gene regulatory mechanism in bacteria. A typical TCS is comprised of a histidine kinase (HK) and a partner response regulator (RR). Specific environment signals lead to autophosphorylation of different HKs, which in turn act as phosphoryl donors for autophosphorylation of their partner RRs. Nonpartner HKs and RRs also interact, giving rise to cross regulation among TCSs in response to diverse signals.PhoR (HK) and PhoB (RR) constitute the TCS for detection of environmental (extracellular) inorganic phosphate (P i ). The PhoR/PhoB TCS controls the expression of a large number of genes for acquisition of alternative phosphorus sources, including phoA, which encodes the non-specific phosphohydrolase bacterial alkaline phosphatase (Bap). Cross activation of PhoB by the nonpartner HK CreC is now a classic example of cross regulation among TCSs. A systematic search for other cross talking HKs revealed five additional HKs that activate (phosphorylate) PhoB (J. M. B. and B. L. W., unpublished data).Examination of cross activation of PhoB by these non-partner HKs by flow cytometry at the single-cell level revealed a bimodal, "all-or-none," distribution pattern for expression of a phoAp-gfp (green fluorescent protein) reporter fusion. Although the basis of the observed stochastic behavior is unclear, it seems to reflect an inherent property of TCSs. We propose that cells exploit the stochastic character of TCSs to achieve nongenetic (epigenetic) diversity within genetically homogeneous cell populations in order to facilitate adaptation to environmental changes.

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Identification of UvrY as the Cognate Response Regulator for the BarA Sensor Kinase in Escherichia coli

Abstract: BarA is a membrane-associated protein that belongs to a subclass of tripartite sensors of the two-component signal transduction system family. In this study, we report that UvrY is the cognate response regulator for BarA of Escherichia coli.

Cited by 153 publications

References 46 publications

Assigning numbers to the arrows: Parameterizing a gene regulation network by using accurate expression kinetics

Assigning numbers to the arrows: Parameterizing a gene regulation network by using accurate expression kinetics

Regulation of Bacterial Virulence by Csr (Rsm) Systems

Stochastic activation of the response regulator PhoB by noncognate histidine kinases

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