Ligand-Induced Asymmetry in Histidine Sensor Kinase Complex Regulates Quorum Sensing

ABSTRACT We corrected the previously published sequence for theregB gene, which encodes a histidine sensor kinase inRhodobacter capsulatus. The deduced RegB amino acid sequence has an additional putative transmembrane domain at the N terminus. Analysis of RegB-PhoA and RegB-LacZ fusion proteins supports a topology model for RegB with six membrane-spanning domains.

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Timing Is Everything: Impact of Naturally Occurring Staphylococcus aureus AgrC Cytoplasmic Domain Adaptive Mutations on Autoinduction

Journal of Bacteriology ◽

10.1128/jb.00409-19 ◽

2019 ◽

Vol 201 (20) ◽

Cited By ~ 5

Author(s):

Tim J. Sloan ◽

Ewan Murray ◽

Maho Yokoyama ◽

Ruth C. Massey ◽

Weng C. Chan ◽

...

Keyword(s):

Molecular Structure ◽

Staphylococcus Aureus ◽

Quorum Sensing ◽

Binding Site ◽

Conformational Changes ◽

Cytoplasmic Domain ◽

Atp Binding ◽

Sensor Kinase ◽

Content Type ◽

Naturally Occurring

ABSTRACT Mutations in the polymorphic Staphylococcus aureus agr locus responsible for quorum sensing (QS)-dependent virulence gene regulation occur frequently during host adaptation. In two genomically closely related S. aureus clinical isolates exhibiting marked differences in Panton-Valentine leukocidin production, a mutation conferring an N267I substitution was identified in the cytoplasmic domain of the QS sensor kinase, AgrC. This natural mutation delayed the onset and accumulation of autoinducing peptide (AIP) and showed reduced responsiveness to exogenous AIPs. Other S. aureus strains harboring naturally occurring AgrC cytoplasmic domain mutations were identified, including T247I, I311T, A343T, L245S, and F264C. These mutations were associated with reduced cytotoxicity, delayed/reduced AIP production, and impaired sensitivity to exogenous AIP. Molecular dynamics simulations were used to model the AgrC cytoplasmic domain conformational changes arising. Although mutations were localized in different parts of the C-terminal domain, their impact on molecular structure was manifested by twisting of the leading helical hairpin α1-α2, accompanied by repositioning of the H-box and G-box, along with closure of the flexible loop connecting the two and occlusion of the ATP-binding site. Such conformational rearrangements of key functional subdomains in these mutants highlight the cooperative response of molecular structure involving dimerization and ATP binding and phosphorylation, as well as the binding site for the downstream response element AgrA. These appear to increase the threshold for agr activation via AIP-dependent autoinduction, thus reducing virulence and maintaining S. aureus in an agr-downregulated “colonization” mode. IMPORTANCE Virulence factor expression in Staphylococcus aureus is regulated via autoinducing peptide (AIP)-dependent activation of the sensor kinase AgrC, which forms an integral part of the agr quorum sensing system. In response to bound AIP, the cytoplasmic domain of AgrC (AgrC-cyt) undergoes conformational changes resulting in dimerization, autophosphorylation, and phosphotransfer to the response regulator AgrA. Naturally occurring mutations in AgrC-cyt are consistent with repositioning of key functional domains, impairing dimerization and restricting access to the ATP-binding pocket. Strains harboring specific AgrC-cyt mutations exhibit reduced AIP autoinduction efficiency and a timing-dependent attenuation of cytotoxicity which may confer a survival advantage during established infection by promoting colonization while restricting unnecessary overproduction of exotoxins.

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The Role of the QseC Quorum-Sensing Sensor Kinase in Epinephrine-Enhanced Motility and Biofilm Formation by Escherichia coli

Cell Biochemistry and Biophysics ◽

10.1007/s12013-014-9924-5 ◽

2014 ◽

Vol 70 (1) ◽

pp. 391-398 ◽

Cited By ~ 19

Author(s):

Kun Yang ◽

Jun Meng ◽

Yun-chao Huang ◽

Lian-hua Ye ◽

Guang-jian Li ◽

...

Keyword(s):

Escherichia Coli ◽

Quorum Sensing ◽

Biofilm Formation ◽

Sensor Kinase

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Identification of a novel unpaired histidine sensor kinase affecting secondary metabolism and morphological differentiation in Streptomyces acidiscabies ATCC 49003

Folia Microbiologica ◽

10.1007/s12223-015-0383-1 ◽

2015 ◽

Vol 60 (4) ◽

pp. 279-287 ◽

Cited By ~ 1

Author(s):

Ji-Min Park ◽

Sun-Uk Choi

Keyword(s):

Secondary Metabolism ◽

Morphological Differentiation ◽

Sensor Kinase ◽

Streptomyces Acidiscabies ◽

Histidine Sensor Kinase

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Genetic and Mechanistic Analyses of the Periplasmic Domain of the Enterohemorrhagic Escherichia coli QseC Histidine Sensor Kinase

Journal of Bacteriology ◽

10.1128/jb.00861-16 ◽

2017 ◽

Vol 199 (8) ◽

Cited By ~ 12

Author(s):

Christopher T. Parker ◽

Regan Russell ◽

Jacqueline W. Njoroge ◽

Angel G. Jimenez ◽

Ron Taussig ◽

...

Keyword(s):

Escherichia Coli ◽

Amino Acids ◽

Shiga Toxin ◽

Secretion System ◽

Enterohemorrhagic Escherichia Coli ◽

Signaling Cascade ◽

Sensor Kinase ◽

Type Three Secretion System ◽

Histidine Sensor Kinase ◽

Type Three Secretion

ABSTRACT The histidine sensor kinase (HK) QseC senses autoinducer 3 (AI-3) and the adrenergic hormones epinephrine and norepinephrine. Upon sensing these signals, QseC acts through three response regulators (RRs) to regulate the expression of virulence genes in enterohemorrhagic Escherichia coli (EHEC). The QseB, QseF, and KdpE RRs that are phosphorylated by QseC constitute a tripartite signaling cascade having different and overlapping targets, including flagella and motility, the type three secretion system encoded by the locus of enterocyte effacement (LEE), and Shiga toxin. We modeled the tertiary structure of QseC's periplasmic sensing domain and aligned the sequences from 12 different species to identify the most conserved amino acids. We selected eight amino acids conserved in all of these QseC homologues. The corresponding QseC site-directed mutants were expressed and still able to autophosphorylate; however, four mutants demonstrated an increased basal level of phosphorylation. These mutants have differential flagellar, motility, LEE, and Shiga toxin expression phenotypes. We selected four mutants for more in-depth analyses and found that they differed in their ability to phosphorylate QseB, KdpE, and QseF. This suggests that these mutations in the periplasmic sensing domain affected the region downstream of the QseC signaling cascade and therefore can influence which pathway QseC regulates. IMPORTANCE In the foodborne pathogen EHEC, QseC senses AI-3, epinephrine, and norepinephrine, increases its autophosphorylation, and then transfers its phosphate to three RRs: QseB, QseF, and KdpE. QseB controls expression of flagella and motility, KdpE controls expression of the LEE region, and QseF controls the expression of Shiga toxin. This tripartite signaling pathway must be tightly controlled, given that flagella and the type three secretion system (T3SS) are energetically expensive appendages and Shiga toxin expression leads to bacterial cell lysis. Our data suggest that mutations in the periplasmic sensing loop of QseC differentially affect the expression of the three arms of this signaling cascade. This suggests that these point mutations may change QseC's phosphotransfer preferences for its RRs.

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Inter-Kingdom Signaling of Stress Hormones: Sensing, Transport and Modulation of Bacterial Physiology

Frontiers in Microbiology ◽

10.3389/fmicb.2021.690942 ◽

2021 ◽

Vol 12 ◽

Author(s):

Amine Mohamed Boukerb ◽

Melyssa Cambronel ◽

Sophie Rodrigues ◽

Ouiza Mesguida ◽

Rikki Knowlton ◽

...

Keyword(s):

Biofilm Formation ◽

Stress Hormones ◽

Sensor Kinase ◽

Gram Negative Bacteria ◽

Physical Effort ◽

Bacterial Physiology ◽

E Coli ◽

Gram Positive Bacteria ◽

Serovar Typhimurium ◽

Histidine Sensor Kinase

Prokaryotes and eukaryotes have coexisted for millions of years. The hormonal communication between microorganisms and their hosts, dubbed inter-kingdom signaling, is a recent field of research. Eukaryotic signals such as hormones, neurotransmitters or immune system molecules have been shown to modulate bacterial physiology. Among them, catecholamines hormones epinephrine/norepinephrine, released during stress and physical effort, or used therapeutically as inotropes have been described to affect bacterial behaviors (i.e., motility, biofilm formation, virulence) of various Gram-negative bacteria (e.g., Escherichia coli, Salmonella enterica serovar Typhimurium, Pseudomonas aeruginosa, Vibrio sp.). More recently, these molecules were also shown to influence the physiology of some Gram-positive bacteria like Enterococcus faecalis. In E. coli and S. enterica, the stress-associated mammalian hormones epinephrine and norepinephrine trigger a signaling cascade by interacting with the QseC histidine sensor kinase protein. No catecholamine sensors have been well described yet in other bacteria. This review aims to provide an up to date report on catecholamine sensors in eukaryotes and prokaryotes, their transport, and known effects on bacteria.

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