Application of comparative genomics in the identification and analysis of novel families of membrane-associated receptors in bacteria

Anantharaman, Vivek; Aravind, L.

doi:10.1186/1471-2164-4-34

Cited by 82 publications

(82 citation statements)

References 76 publications

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“…5, which is published as supporting information on the PNAS web site. In addition to the GGDEF͞EAL domains, all of the recognizable domains in these DGC and PDE domaincontaining proteins are involved in signal transduction and include the PAS and PAC domains, implicated in heme binding: a CheY-like response regulator domain, a member of the CHASE family of extracellular domains; a HAMP domain, found as a linker between various receptor domains and signaltransducing protein (21); the MHYT domain, which is often found at the N terminus of proteins that are part of signal transduction pathways (22); and a protein with a 7TMR-DISMED2͞7TMR-DISM 7TM (seven-transmembrane receptor with diverse intracellular signaling module) domain at its N terminus, implicated in the sensing of external carbohydrates (23). Collectively, these structural features suggest that all of these proteins are involved in signal transduction and most likely function in the synthesis or hydrolysis of c-di-GMP after reception of signals that stimulate enzymatic activity.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Kulesekara¹,

Lee²,

Brencic³

et al. 2006

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

506

613

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The opportunistic pathogen Pseudomonas aeruginosa is responsible for systemic infections in immunocompromised individuals and chronic respiratory disease in patients with cystic fibrosis. Cyclic nucleotides are known to play a variety of roles in the regulation of virulence-related factors in pathogenic bacteria. A set of P. aeruginosa genes, encoding proteins that contain putative domains characteristic of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs) that are responsible for the maintenance of cellular levels of the second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) was identified in the annotated genomes of P. aeruginosa strains PAO1 and PA14. Although the majority of these genes are components of the P. aeruginosa core genome, several are located on presumptive horizontally acquired genomic islands. A comprehensive analysis of P. aeruginosa genes encoding the enzymes of c-di-GMP metabolism (DGC- and PDE-encoding genes) was carried out to analyze the function of c-di-GMP in two disease-related phenomena, cytotoxicity and biofilm formation. Analysis of the phenotypes of DGC and PDE mutants and overexpressing clones revealed that certain virulence-associated traits are controlled by multiple DGCs and PDEs through alterations in c-di-GMP levels. A set of mutants in selected DGC- and PDE-encoding genes exhibited attenuated virulence in a mouse infection model. Given that insertions in different DGC and PDE genes result in distinct phenotypes, it seems likely that the formation or degradation of c-di-GMP by these enzymes is in highly localized and intimately linked to particular targets of c-di-GMP action.

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Section: Resultsmentioning

confidence: 99%

Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Kulesekara¹,

Lee²,

Brencic³

et al. 2006

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

506

613

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“…The precise nature of the input signals for the RetS͞LadS pathway is unknown at this time, as is the signal received by GacS. The 7TMR-DISMED2 domains found in RetS and LadS have been identified in a variety of carbohydrate binding proteins (29), suggesting that both hybrid sensors sense carbohydrates present in host tissue, which can serve to direct the course of infection. Alternatively, the carbohydrates sensed by RetS and LadS may be produced by P. aeruginosa and therefore can represent a novel form of quorum sensing.…”

Section: Discussionmentioning

confidence: 99%

“…LadS and RetS contain 7TMR-DISMED2 periplasmic sensor modules, which show a modest 35% sequence identity, suggesting that they bind related but nonidentical ligands. This domain has been predicted to bind carbohydrates and is always associated with a transmembrane domain (7TM-DISM) (29). Activation of LadS or RetS, however, has reciprocal effects on a shared set of positively and negatively regulated virulence determinants.…”

Section: Discussionmentioning

confidence: 99%

Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes

Ventre

Goodman²,

Vallet-Gély³

et al. 2005

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

381

461

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The opportunistic pathogen Pseudomonas aeruginosa is responsible for a wide range of acute and chronic infections. The transition to chronic infections is accompanied by physiological changes in the bacteria favoring formation of biofilm communities. Here we report the identification of LadS, a hybrid sensor kinase that controls the reciprocal expression of genes for type III secretion and biofilm-promoting polysaccharides. Domain organization of LadS and the range of LadS-controlled genes suggest that it counteracts the activities of another sensor kinase, RetS. These two pathways converge by controlling the transcription of a small regulatory RNA, RsmZ. This work identifies a previously undescribed signal transduction network in which the activities of signal-receiving sensor kinases LadS, RetS, and GacS regulate expression of virulence genes associated with acute or chronic infection by transcriptional and posttranscriptional mechanisms.biofilm ͉ pel genes ͉ small RNA ͉ two-component system ͉ type III secretion

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“…Bioinformatics analyses (using the programs TMHMM, MEMSAT3, and OCTOPUS [9][10][11]) indicated the presence of at least six transmembrane helices in the YpdA input domain, which belongs to the 5TM Lyt (LytS-YhcK) type (Fig. 1A) (7). In addition, YpdA harbors a GAF domain, also found in cyclic GMP-specific phosphodiesterases, adenylyl cyclases, and FhlA (hence GAF).…”

mentioning

confidence: 99%

Identification of a Target Gene and Activating Stimulus for the YpdA/YpdB Histidine Kinase/Response Regulator System in Escherichia coli

Fried¹,

Behr²,

Jung³

2012

Journal of Bacteriology

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Escherichia coli contains 30 two-component systems (TCSs), each consisting of a histidine kinase and a response regulator. Whereas most TCSs are well characterized in this model organism, little is known about the YpdA/YpdB system. To identify YpdB-regulated genes, we compared the transcriptomes of E. coli cells overproducing either YpdB or a control protein. Expression levels of 15 genes differed by more than 1.9-fold between the two strains. A comprehensive evaluation of these genes identified yhjX as the sole target of YpdB. Electrophoretic mobility shift assays with purified YpdB confirmed its interaction with the yhjX promoter. Specifically, YpdB binds to two direct repeats of the motif GGCATTTCAT separated by an 11-bp spacer in the yhjX promoter. yhjX encodes a cytoplasmic membrane protein of unknown function that belongs to the major facilitator superfamily of transporters. Finally, we characterized the pattern of yhjX expression and identified extracellular pyruvate as a stimulus for the YpdA/YpdB system. It is suggested that YpdA/YpdB contributes to nutrient scavenging before entry into stationary phase.

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Application of comparative genomics in the identification and analysis of novel families of membrane-associated receptors in bacteria

Cited by 82 publications

References 76 publications

Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes

Identification of a Target Gene and Activating Stimulus for the YpdA/YpdB Histidine Kinase/Response Regulator System in Escherichia coli

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