Phylogenetic analysis of quorum sensing systems in bacteria

AbstractQuorum sensing (QS) is a cell-to-cell communication system that enables bacteria to coordinate their gene expression depending on their population density, via the detection of small molecules called autoinducers. In this way bacteria can act collectively to initiate processes like bioluminescence, virulence and biofilm formation. Autoinducers are detected by receptors, some of which are part of Two Component Signal Transduction Systems (TCS), which comprise of a sensor histidine kinase (usually membrane-bound) and a cognate response regulator. Different QS systems are used by different bacterial taxa, and their relative evolutionary relationships have not been extensively studied. To address this, we used the KEGG database to identify all the QS receptors and response regulators that are part of TCS and collected their amino acid sequences from different species. In order to discover their evolutionary relationships: (i) we compared the combinations of the highly conserved domains in the different receptors and response regulators using the SMART and KEGG databases, and (ii) we constructed and compared phylogenetic trees, based on neighbor-joining and maximum likelihood methods. For both the QS receptors and the response regulators, our analysis indicates certain close evolutionary relationships, highlight a common evolutionary history, and which can inform future applications, such as the design of novel inhibitors for pathogenic QS systems.

Evolution of two-component quorum sensing systems

Access Microbiology ◽

10.1099/acmi.0.000303 ◽

2022 ◽

Vol 4 (1) ◽

Author(s):

Marina Giannakara ◽

Vassiliki Lila Koumandou

Keyword(s):

Quorum Sensing ◽

Response Regulator ◽

Phylogenetic Analyses ◽

Cell Communication ◽

Evolutionary Relationships ◽

Response Regulators ◽

Modular Architecture ◽

Two Component ◽

Quorum sensing (QS) is a cell-to-cell communication system that enables bacteria to coordinate their gene expression depending on their population density, via the detection of small molecules called autoinducers. In this way bacteria can act collectively to initiate processes like bioluminescence, virulence and biofilm formation. Autoinducers are detected by receptors, some of which are part of two-component signal transduction systems (TCS), which comprise of a (usually membrane-bound) sensor histidine kinase (HK) and a cognate response regulator (RR). Different QS systems are used by different bacterial taxa, and their relative evolutionary relationships have not been extensively studied. To address this, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to identify all the QS HKs and RRs that are part of TCSs and examined their conservation across microbial taxa. We compared the combinations of the highly conserved domains in the different families of receptors and response regulators using the Simple Modular Architecture Research Tool (SMART) and KEGG databases, and we also carried out phylogenetic analyses for each family, and all families together. The distribution of the different QS systems across taxa, indicates flexibility in HK–RR pairing and highlights the need for further study of the most abundant systems. For both the QS receptors and the response regulators, our results indicate close evolutionary relationships between certain families, highlighting a common evolutionary history which can inform future applications, such as the design of novel inhibitors for pathogenic QS systems.

Cpx Two-Component Signal Transduction inEscherichia coli: Excessive CpxR-P Levels Underlie CpxA* Phenotypes

10.1128/jb.182.5.1423-1426.2000 ◽

2000 ◽

Vol 182 (5) ◽

pp. 1423-1426 ◽

Cited By ~ 32

Author(s):

Peter De Wulf ◽

E. C. C. Lin

Keyword(s):

Signal Transduction ◽

Response Regulator ◽

Response Regulators ◽

Signal Transduction System ◽

Regulate Gene Expression ◽

Adverse Conditions ◽

Two Component ◽

Sensor Protein ◽

ABSTRACT In Escherichia coli, the CpxA-CpxR two-component signal transduction system and the ςE and ς32response pathways jointly regulate gene expression in adaptation to adverse conditions. These include envelope protein distress, heat shock, oxidative stress, high pH, and entry into stationary phase. Certain mutant versions of the CpxA sensor protein (CpxA* proteins) exhibit an elevated ratio of kinase to phosphatase activity on CpxR, the cognate response regulator. As a result, CpxA* strains display numerous phenotypes, many of which cannot be easily related to currently known functions of the CpxA-CpxR pathway. It is unclear whether CpxA* phenotypes are caused solely by hyperphosphorylation of CpxR. We here report that all of the tested CpxA* phenotypes depend on elevated levels of CpxR-P and not on cross-signalling of CpxA* to noncognate response regulators.

Evolutionary relationships of completely sequenced Clostridia species and close relatives

INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY ◽

10.1099/ijsem.0.000638 ◽

2015 ◽

Vol 65 (Pt_11) ◽

pp. 4276-4283 ◽

Cited By ~ 12

Author(s):

Takashi Kunisawa

Keyword(s):

Maximum Likelihood ◽

Phylogenetic Trees ◽

Gene Arrangement ◽

Evolutionary Relationships ◽

Rrna Gene ◽

Sequence Information ◽

Bayesian Tree ◽

Maximum Likelihood Methods ◽

Genome Sequence Information ◽

Close Relatives

The class Clostridia in the phylum Firmicutes includes a very heterogeneous assemblage of bacteria. Their evolutionary relationships are not well established; revisions of their phylogenetic placements based on comparative studies of 16S rRNA gene sequences are in progress as genome sequence information accumulates. In this work, phylogenetic trees were reconstructed based on 21 concatenated ribosomal protein sequences using Bayesian and maximum-likelihood methods. Both trees consistently indicate that the Halanaerobiales is a deeply branching order among the class Clostridia. The rest of the Clostridia species are grouped into 10 monophyletic clusters, most of which are comprised of two or three orders and families according to the current Clostridial taxonomy. The maximum-likelihood tree placed Coprothermobacter proteolyticus and Thermodesulfobium narugense in the class Clostridia in accordance with the current taxonomy, in which these two bacteria are assigned to the family Thermodesulfobiaceae. However, the Bayesian tree placed these two bacteria at the boundary between the Firmicutes and Actinobacteria. A gene arrangement that is present uniquely in the Firmicutes species was identified. Both Coprothermobacter proteolyticus and Thermodesulfobium narugense do not have this arrangement characteristic of the Firmicutes. On the basis of the Bayesian tree and gene arrangement comparison, it is suggested that Coprothermobacter proteolyticus and Thermodesulfobium narugense should be placed outside the phylum Firmicutes.

Histidine kinases in signal transduction pathways of eukaryotes

Journal of Cell Science ◽

10.1242/jcs.110.10.1141 ◽

1997 ◽

Vol 110 (10) ◽

pp. 1141-1145 ◽

Cited By ~ 2

Author(s):

W.F. Loomis ◽

G. Shaulsky ◽

N. Wang

Keyword(s):

Signal Transduction ◽

Response Regulator ◽

Signal Transduction Pathways ◽

Response Regulators ◽

Histidine Kinases ◽

Camp Phosphodiesterase ◽

Wide Range ◽

Two Component ◽

Dependent Protein

Autophosphorylating histidine kinases are an ancient conserved family of enzymes that are found in eubacteria, archaebacteria and eukaryotes. They are activated by a wide range of extracellular signals and transfer phosphate moieties to aspartates found in response regulators. Recent studies have shown that such two-component signal transduction pathways mediate osmoregulation in Saccharomyces cerevisiae, Dictyostelium discoideum and Neurospora crassa. Moreover, they play pivotal roles in responses of Arabidopsis thaliana to ethylene and cytokinin. A transmembrane histidine kinase encoded by dhkA accumulates when Dictyostelium cells aggregate during development. Activation of DhkA results in the inhibition of its response regulator, RegA, which is a cAMP phosphodiesterase that regulates the cAMP dependent protein kinase PKA. When PKA is activated late in the differentiation of prespore cells, they encapsulate into spores. There is evidence that this two-component system participates in a feedback loop linked to PKA in prestalk cells such that the signal to initiate encapsulation is rapidly amplified. Such signal transduction pathways can be expected to be found in a variety of eukaryotic differentiations since they are rapidly reversible and can integrate disparate signals.

The RapP-PhrP Quorum-Sensing System of Bacillus subtilis Strain NCIB3610 Affects Biofilm Formation through Multiple Targets, Due to an Atypical Signal-Insensitive Allele of RapP

10.1128/jb.02382-14 ◽

2014 ◽

Vol 197 (3) ◽

pp. 592-602 ◽

Cited By ~ 42

Author(s):

Shira Omer Bendori ◽

Shaul Pollak ◽

Dorit Hizi ◽

Avigdor Eldar

Keyword(s):

Bacillus Subtilis ◽

Quorum Sensing ◽

Biofilm Formation ◽

Response Regulator ◽

Subtilis Strain ◽

Transcriptional Level ◽

Response Regulators ◽

Multiple Targets ◽

Content Type ◽

Negative Effect

The genome ofBacillus subtilis168 encodes eightrap-phrquorum-sensing pairs. Rap proteins of all characterized Rap-Phr pairs inhibit the function of one or several important response regulators: ComA, Spo0F, or DegU. This inhibition is relieved upon binding of the peptide encoded by the cognatephrgene.Bacillus subtilisstrain NCIB3610, the biofilm-proficient ancestor of strain 168, encodes, in addition, therapP-phrPpair on the plasmid pBS32. RapP was shown to dephosphorylate Spo0F and to regulate biofilm formation, but unlike other Rap-Phr pairs, RapP does not interact with PhrP. In this work we extend the analysis of the RapP pathway by reexamining its transcriptional regulation, its effect on downstream targets, and its interaction with PhrP. At the transcriptional level, we show thatrapPandphrPregulation is similar to that of otherrap-phrpairs. We further find that RapP has an Spo0F-independent negative effect on biofilm-related genes, which is mediated by the response regulator ComA. Finally, we find that the insensitivity of RapP to PhrP is due to a substitution of a highly conserved residue in the peptide binding domain of therapPallele of strain NCIB3610. Reversing this substitution to the consensus amino acid restores the PhrP dependence of RapP activity and eliminates the effects of therapP-phrPlocus on ComA activity and biofilm formation. Taken together, our results suggest that RapP strongly represses biofilm formation through multiple targets and that PhrP does not counteract RapP due to a rare mutation inrapP.

Constitutive Activation of Two-Component Response Regulators: Characterization of VirG Activation in Agrobacterium tumefaciens

10.1128/jb.00387-06 ◽

2006 ◽

Vol 188 (14) ◽

pp. 5204-5211 ◽

Cited By ~ 15

Author(s):

Rong Gao ◽

Aindrila Mukhopadhyay ◽

Fang Fang ◽

David G. Lynn

Keyword(s):

Agrobacterium Tumefaciens ◽

Conformational Changes ◽

Response Regulator ◽

Structural Features ◽

Response Regulators ◽

Two Component System ◽

Plant Host ◽

Two Component ◽

Two Component Signal Transduction

ABSTRACT Response regulators are the ultimate modulators in two-component signal transduction pathways. The N-terminal receiver domains generally accept phosphates from cognate histidine kinases to control output. VirG for example, the response regulator of the VirA/VirG two-component system in Agrobacterium tumefaciens, mediates the expression of virulence genes in response to plant host signals. Response regulators have a highly conserved structure and share a similar conformational activation upon phosphorylation, yet the sequence and structural features that determine or perturb the cooperative activation events are ill defined. Here we use VirG and the unique features of the Agrobacterium system to extend our understanding of the response regulator activation. Two previously isolated constitutive VirG mutants, VirGN54D and VirGI77V/D52E, provide the foundation for our studies. In vivo phosphorylation patterns establish that VirGN54D is able to accumulate phosphates from small-molecule phosphate donors, such as acetyl phosphate, while the VirGI77V/D52E allele carries conformational changes mimicking the active conformation. Further structural alterations on these two alleles begin to reveal the changes necessary for response regulator activation.

Identification and Functional and Spectral Characterization of a Globin-coupled Histidine Kinase from Anaeromyxobacter sp. Fw109-5

Journal of Biological Chemistry ◽

10.1074/jbc.m111.274811 ◽

2011 ◽

Vol 286 (41) ◽

pp. 35522-35534 ◽

Cited By ~ 30

Author(s):

Kenichi Kitanishi ◽

Kazuo Kobayashi ◽

Takeshi Uchida ◽

Koichiro Ishimori ◽

Jotaro Igarashi ◽

...

Keyword(s):

Histidine Kinase ◽

Oxygen Sensor ◽

Response Regulator ◽

Dissociation Rate ◽

Amino Acid Sequences ◽

Site Directed Mutagenesis ◽

Significant Activity ◽

Distal Side ◽

First Time

Two-component signal transduction systems regulate numerous important physiological functions in bacteria. In this study we have identified, cloned, overexpressed, and characterized a dimeric full-length heme-bound (heme:protein, 1:1 stoichiometry) globin-coupled histidine kinase (AfGcHK) from Anaeromyxobacter sp. strain Fw109-5 for the first time. The Fe(III), Fe(II)-O2, and Fe(II)-CO complexes of the protein displayed autophosphorylation activity, whereas the Fe(II) complex had no significant activity. A H99A mutant lost heme binding ability, suggesting that this residue is the heme proximal ligand. Moreover, His-183 was proposed as the autophosphorylation site based on the finding that the H183A mutant protein was not phosphorylated. The phosphate group of autophosphorylated AfGcHK was transferred to Asp-52 and Asp-169 of a response regulator, as confirmed from site-directed mutagenesis experiments. Based on the amino acid sequences and crystal structures of other globin-coupled oxygen sensor enzymes, Tyr-45 was assumed to be the O2 binding site at the heme distal side. The O2 dissociation rate constant, 0.10 s−1, was substantially increased up to 8.0 s−1 upon Y45L mutation. The resonance Raman frequencies representing νFe-O2 (559 cm−1) and νO-O (1149 cm−1) of the Fe(II)-O2 complex of Y45F mutant AfGcHK were distinct from those of the wild-type protein (νFe-O2, 557 cm−1; νO-O, 1141 cm−1), supporting the proposal that Tyr-45 is located at the distal side and forms hydrogen bonds with the oxygen molecule bound to the Fe(II) complex. Thus, we have successfully identified and characterized a novel heme-based globin-coupled oxygen sensor histidine kinase, AfGcHK, in this study.

Conversion of Norepinephrine to 3,4-Dihdroxymandelic Acid in Escherichia coli Requires the QseBC Quorum-Sensing System and the FeaR Transcription Factor

10.1128/jb.00564-17 ◽

2017 ◽

Vol 200 (1) ◽

Cited By ~ 1

Author(s):

Sasikiran Pasupuleti ◽

Nitesh Sule ◽

Michael D. Manson ◽

Arul Jayaraman

Keyword(s):

Escherichia Coli ◽

Transcription Factor ◽

Quorum Sensing ◽

Aromatic Amines ◽

Response Regulator ◽

Content Type ◽

E Coli ◽

Expression Of Genes ◽

K 12 ◽

ABSTRACTThe detection of norepinephrine (NE) as a chemoattractant byEscherichia colistrain K-12 requires the combined action of the TynA monoamine oxidase and the FeaB aromatic aldehyde dehydrogenase. The role of these enzymes is to convert NE into 3,4-dihydroxymandelic acid (DHMA), which is a potent chemoattractant sensed by the Tsr chemoreceptor. These two enzymes must be induced by prior exposure to NE, and cells that are exposed to NE for the first time initially show minimal chemotaxis toward it. The induction of TynA and FeaB requires the QseC quorum-sensing histidine kinase, and the signaling cascade requires new protein synthesis. Here, we demonstrate that the cognate response regulator for QseC, the transcription factor QseB, is also required for induction. The related quorum-sensing kinase QseE appears not to be part of the signaling pathway, but its cognate response regulator, QseF, which is also a substrate for phosphotransfer from QseC, plays a nonessential role. The promoter of thefeaRgene, which encodes a transcription factor that has been shown to be essential for the expression oftynAandfeaB, has two predicted QseB-binding sites. One of these sites appears to be in an appropriate position to stimulate transcription from the P1promoter of thefeaRgene. This study unites two well-known pathways: one for expression of genes regulated by catecholamines (QseBC) and one for expression of genes required for metabolism of aromatic amines (FeaR, TynA, and FeaB). This cross talk allowsE. colito convert the host-derived and chemotactically inert NE into the potent bacterial chemoattractant DHMA.IMPORTANCEThe chemotaxis ofE. coliK-12 to norepinephrine (NE) requires the conversion of NE to 3,4-dihydroxymandleic acid (DHMA), and DHMA is both an attractant and inducer of virulence gene expression for a pathogenic enterohemorrhagicE. coli(EHEC) strain. The induction of virulence by DHMA and NE requires QseC. The results described here show that the cognate response regulator for QseC, QseB, is also required for conversion of NE into DHMA. Production of DHMA requires induction of a pathway involved in the metabolism of aromatic amines. Thus, the QseBC sensory system provides a direct link between virulence and chemotaxis, suggesting that chemotaxis to host signaling molecules may require that those molecules are first metabolized by bacterial enzymes to generate the actual chemoattractant.

Look who's talking: communication and quorum sensing in the bacterial world

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2007.2039 ◽

2007 ◽

Vol 362 (1483) ◽

pp. 1119-1134 ◽

Cited By ~ 509

Author(s):

Paul Williams ◽

Klaus Winzer ◽

Weng C Chan ◽

Miguel Cámara

Keyword(s):

Quorum Sensing ◽

Bacterial Population ◽

Response Regulator ◽

Cell Communication ◽

Threshold Concentration ◽

Critical Threshold ◽

Signal Molecules ◽

Bacterial Cells ◽

Environmental Threats ◽

Generic Term

For many years bacteria were considered primarily as autonomous unicellular organisms with little capacity for collective behaviour. However, we now appreciate that bacterial cells are in fact, highly communicative. The generic term ‘quorum sensing’ has been adopted to describe the bacterial cell-to-cell communication mechanisms which co-ordinate gene expression usually, but not always, when the population has reached a high cell density. Quorum sensing depends on the synthesis of small molecules (often referred to as pheromones or autoinducers) that diffuse in and out of bacterial cells. As the bacterial population density increases, so does the synthesis of quorum sensing signal molecules, and consequently, their concentration in the external environment rises. Once a critical threshold concentration has been reached, a target sensor kinase or response regulator is activated (or repressed) so facilitating the expression of quorum sensing-dependent genes. Quorum sensing enables a bacterial population to mount a co-operative response that improves access to nutrients or specific environmental niches, promotes collective defence against other competitor prokaryotes or eukaryotic defence mechanisms and facilitates survival through differentiation into morphological forms better able to combat environmental threats. Quorum sensing also crosses the prokaryotic–eukaryotic boundary since quorum sensing-dependent signalling can be exploited or inactivated by both plants and mammals.

Systematic Inactivation and Phenotypic Characterization of Two-Component Signal Transduction Systems of Enterococcus faecalis V583

10.1128/jb.186.23.7951-7958.2004 ◽

2004 ◽

Vol 186 (23) ◽

pp. 7951-7958 ◽

Cited By ~ 103

Author(s):

Lynn E. Hancock ◽

Marta Perego

Keyword(s):

Signal Transduction ◽

Antibiotic Resistance ◽

Environmental Stress ◽

Enterococcus Faecalis ◽

Response Regulator ◽

Phenotypic Characterization ◽

Response Regulators ◽

Two Component ◽

Biofilm Development

ABSTRACT The ability of enterococci to adapt and respond to different environmental stimuli, including the host environment, led us to investigate the role of two-component signal transduction in the regulation of Enterococcus faecalis physiology. Using a bioinformatic approach, we previously identified 17 two-component systems (TCS), consisting of a sensory histidine kinase and the cognate response regulator, as well as an additional orphan response regulator (L. E. Hancock and M. Perego, J. Bacteriol. 184:5819-5825, 2002). In an effort to identify the potential function of each TCS in the biology of E. faecalis clinical isolate strain V583, we constructed insertion mutations in each of the response regulators. We were able to inactivate 17 of 18 response regulators, the exception being an ortholog of YycF, previously shown to be essential for viability in a variety of gram-positive microorganisms. The biological effects of the remaining mutations were assessed by using a number of assays, including antibiotic resistance, biofilm formation, and environmental stress. We identified TCS related to antibiotic resistance and environmental stress and found one system which controls the initiation of biofilm development by E. faecalis.