The Brucella abortus General Stress Response System Regulates Chronic Mammalian Infection and Is Controlled by Phosphorylation and Proteolysis

Kim, Hyesook; Caswell, Clayton C.; Foreman, Robert T.; Roop, R. Martin; Crosson, Sean

doi:10.1074/jbc.m113.459305

Cited by 68 publications

(124 citation statements)

References 43 publications

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“…Because PhyR uses a degenerate N-terminal sigma factor-like output domain to compete with σ EcfG for NepR binding, this partner switch was coined "sigma factor mimicry" (1). The importance of the alphaproteobacterial GSR in natural environments is underlined by several studies demonstrating its requirement for survival and competitiveness in the phyllosphere in Sphingomonas melonis (10) and Methylobacterium extorquens (8), the establishment of symbiotic interactions in Bradyrhizobium japonicum (9), and host-pathogen interactions in Brucella (6,11) and Bartonella (3) species.…”

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confidence: 99%

“…In Alphaproteobacteria, the GSR is controlled by an alternative extracytoplasmic function (ECF) sigma factor, usually called σ EcfG (1) or ECF15 sigma factor (2), the activity of which is regulated by a conserved partner-switching mechanism (1,(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In unstressed conditions, σ EcfG is sequestered by its anti-sigma factor NepR.…”

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confidence: 99%

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Complex two-component signaling regulates the general stress response in Alphaproteobacteria

Kaczmarczyk¹,

Hochstrasser²,

Vorholt³

et al. 2014

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

117

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Significance Bacteria possess many regulatory systems to monitor their environment and adapt their physiology accordingly. Whereas most systems sense one specific signal, the general stress response (GSR) is activated by many signals and protects cells against a wide range of adverse conditions. In Alphaproteobacteria, the GSR is controlled by the response regulator PhyR, but little is known about the upstream pathways. Here, we establish the GSR as a complex regulatory network composed of a particular family of partially redundant sensor kinases and of additional response regulators that modulate PhyR activity in Sphingomonas melonis . Given the broad conservation of this kinase family, it is possible that it plays a general role in the GSR in Alphaproteobacteria.

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confidence: 99%

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confidence: 99%

Complex two-component signaling regulates the general stress response in Alphaproteobacteria

Kaczmarczyk¹,

Hochstrasser²,

Vorholt³

et al. 2014

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

117

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“…strain Fr1, Brucella abortus, and Bartonella quintana (15,16,18,19,21,(23)(24)(25)(26)(27). These mechanisms appear to be conserved, with some species-specific variations, and the current common model can be summarized as follows ( Fig.…”

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confidence: 99%

“…Accordingly, rpoE2 mutants have been found to be more sensitive than the wild-type strain to desiccation and osmotic stress, as well as heat and oxidative stress in the stationary phase (6-8, 11). RpoE2 orthologues, collectively called EcfG or ECF15 sigma factors (12), are widely distributed among Alphaproteobacteria, and several of them have been described as activated under stress or starvation conditions and to play various roles in stress resistance and/or host colonization (13)(14)(15)(16)(17)(18)(19)(20)(21)(22).The mechanisms of activation of EcfG sigma factors in response to stress have been studied in several bacteria, including Methylobacterium extorquens, Bradyrhizobium japonicum, S. meliloti, Caulobacter crescentus, Sphingomonas sp. strain Fr1, Brucella abortus, and Bartonella quintana (15,16,18,19,21,[23][24][25][26][27].…”

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confidence: 99%

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confidence: 99%

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A Putative Bifunctional Histidine Kinase/Phosphatase of the HWE Family Exerts Positive and Negative Control on the Sinorhizobium meliloti General Stress Response

Sauviac

Bruand

2014

J Bacteriol

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The EcfG-type sigma factor RpoE2 is the regulator of the general stress response in Sinorhizobium meliloti. RpoE2 activity is negatively regulated by two NepR-type anti-sigma factors (RsiA1/A2), themselves under the control of two anti-anti-sigma factors (RsiB1/B2) belonging to the PhyR family of response regulators. The current model of RpoE2 activation suggests that in response to stress, RsiB1/B2 are activated by phosphorylation of an aspartate residue in their receiver domain. Once activated, RsiB1/B2 become able to interact with the anti-sigma factors and release RpoE2, which can then associate with the RNA polymerase to transcribe its target genes. The purpose of this work was to identify and characterize proteins involved in controlling the phosphorylation status of RsiB1/B2. Using in vivo approaches, we show that the putative histidine kinase encoded by the rsiC gene (SMc01507), located downstream from rpoE2, is able to both positively and negatively regulate the general stress response. In addition, our data suggest that the negative action of RsiC results from inhibition of RsiB1/B2 phosphorylation. From these observations, we propose that RsiC is a bifunctional histidine kinase/phosphatase responsible for RsiB1/B2 phosphorylation or dephosphorylation in the presence or absence of stress, respectively. Two proteins were previously proposed to control PhyR phosphorylation in Caulobacter crescentus and Sphingomonas sp. strain FR1. However, these proteins contain a Pfam: HisKA_2 domain of dimerization and histidine phosphotransfer, whereas S. meliloti RsiC harbors a Pfam:HWE_HK domain instead. Therefore, this is the first report of an HWE_HK-containing protein controlling the general stress response in Alphaproteobacteria. Bacteria naturally live in constantly changing environments, where they are exposed to many stressful conditions, including nutrient limitation and biotic or abiotic stresses. The capacity to sense and adapt to these stresses is essential for the survival of the bacteria, which have evolved various types of stress responses. A number of these responses function by eliminating the inducing stress and/or repairing the associated cell damage. In parallel to these stress-specific responses, a so-called general stress response is activated under numerous different stress conditions and confers multiple stress resistances to the bacteria.It has been known for a long time that sigma factors play a central role in the control of the general stress response of both Gram-positive and Gram-negative bacteria. In Bacillus subtilis and other firmicutes, this response is controlled by B (1, 2), whereas in Escherichia coli and related Gammaproteobacteria, as well as in several Beta-and Deltaproteobacteria, it is controlled by S (3, 4). However, in the alphaproteobacterial group, the prominent role of extracytoplasmic-function sigma factors was uncovered recently with the finding that RpoE2 controls a general stress response in Sinorhizobium meliloti, the nitrogen-fixing symbiont of alfalfa (5). RpoE2 i...

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Canonical and non‐canonical EcfG sigma factors control the general stress response in Rhizobium etli

et al. 2013

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A core component of the α-proteobacterial general stress response (GSR) is the extracytoplasmic function (ECF) sigma factor EcfG, exclusively present in this taxonomic class. Half of the completed α-proteobacterial genome sequences contain two or more copies of genes encoding σEcfG-like sigma factors, with the primary copy typically located adjacent to genes coding for a cognate anti-sigma factor (NepR) and two-component response regulator (PhyR). So far, the widespread occurrence of additional, non-canonical σEcfG copies has not satisfactorily been explained. This study explores the hierarchical relation between Rhizobium etli σEcfG1 and σEcfG2, canonical and non-canonical σEcfG proteins, respectively. Contrary to reports in other species, we find that σEcfG1 and σEcfG2 act in parallel, as nodes of a complex regulatory network, rather than in series, as elements of a linear regulatory cascade. We demonstrate that both sigma factors control unique yet also shared target genes, corroborating phenotypic evidence. σEcfG1 drives expression of rpoH2, explaining the increased heat sensitivity of an ecfG1 mutant, while katG is under control of σEcfG2, accounting for reduced oxidative stress resistance of an ecfG2 mutant. We also identify non-coding RNA genes as novel σEcfG targets. We propose a modified model for GSR regulation in R. etli, in which σEcfG1 and σEcfG2 function largely independently. Based on a phylogenetic analysis and considering the prevalence of α-proteobacterial genomes with multiple σEcfG copies, this model may also be applicable to numerous other species.

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The Brucella abortus General Stress Response System Regulates Chronic Mammalian Infection and Is Controlled by Phosphorylation and Proteolysis

Cited by 68 publications

References 43 publications

Complex two-component signaling regulates the general stress response in Alphaproteobacteria

Complex two-component signaling regulates the general stress response in Alphaproteobacteria

A Putative Bifunctional Histidine Kinase/Phosphatase of the HWE Family Exerts Positive and Negative Control on the Sinorhizobium meliloti General Stress Response

Canonical and non‐canonical EcfG sigma factors control the general stress response in Rhizobium etli

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