Hierarchical involvement of various GGDEF domain proteins in rdar morphotype development of <i>Salmonella enterica</i> serovar Typhimurium

Kader, Abdul; Simm, Roger; Gerstel, Ulrich; Morr, Michael; Römling, Ute

doi:10.1111/j.1365-2958.2006.05123.x

Cited by 189 publications

(240 citation statements)

References 47 publications

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“…More specifically, the c-di-GMP phosphodiesterase FimX is involved in the assembly of Tfp type IV pili, which are required for twitching motility, biofilm formation, and adherence of Pseudomonas (52). In addition, increased c-di-GMP levels in S. typhimurium are associated with increased curli synthesis (53). Our work revealed yet another virulence factor, type 1 pili, whose expression is regulated via a c-di-GMP-dependent pathway.…”

Section: Discussionmentioning

confidence: 78%

The Flagellar Sigma Factor FliA Regulates Adhesion and Invasion of Crohn Disease-associated Escherichia coli via a Cyclic Dimeric GMP-dependent Pathway

Claret

Miquel

Vieille

et al. 2007

Journal of Biological Chemistry

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The invasion of intestinal epithelial cells by the Crohn disease-associated adherent-invasive Escherichia coli (AIEC) strain LF82 depends on surface appendages, such as type 1 pili and flagella. The absence of flagella in the AIEC strain LF82 results in a concomitant loss of type 1 pili. Here, we show that flagellar regulators, transcriptional activator FlhD 2 C 2 , and sigma factor FliA are involved in the coordination of flagellar and type 1 pili synthesis. In the deletion mutants lacking these regulators, type 1 pili synthesis, adhesion, and invasion were severely decreased. FliA expressed alone in trans was sufficient to restore these defects in both the LF82-⌬flhD and LF82-⌬fliA mutants. We related the loss of type 1 pili to the decreased expression of the FliA-dependent yhjH gene in the LF82-⌬fliA mutant. YhjH is an EAL domain phosphodiesterase involved in degradation of the bacterial second messenger cyclic dimeric GMP (c-di-GMP). Increased expression of either yhjH or an alternative c-di-GMP phosphodiesterase, yahA, partially restored type 1 pili synthesis, adhesion, and invasion in the LF82-⌬fliA mutant. Deletion of the GGDEF domain diguanylate cyclase gene, yaiC, involved in c-di-GMP synthesis in the LF82-⌬fliA mutant also partially restored these defects, whereas overexpression of the c-di-GMP receptor YcgR had the opposite effect. These findings show that in the AIEC strain LF82, FliA is a key regulatory component linking flagellar and type 1 pili synthesis and that its effect on type 1 pili is mediated, at least in part, via a c-di-GMP-dependent pathway.Many virulent bacteria, including Aeromonas caviae (1), Campylobacter jejuni (2), Clostridium difficile (3), Helicobacter pylori (4), Legionella pneumophila (5), Salmonella enterica serovar Typhimurium (6), and Vibrio cholerae (7), use flagellar motility to avoid unfavorable environments and to establish replication niches at different stages of infection. In Enterobacteriaceae, flagellar type III secretion and assembly are strictly dependent on the organization of a hierarchy that controls the sequential expression of structural and regulatory genes. In Escherichia coli and Salmonella typhimurium, the heterotetrameric transcription factor FlhD 2 C 2 (8) is positioned at the top of the flagellar expression hierarchy, where the decision to produce flagella is made (9, 10). The flhDC operon encoding FlhD 2 C 2 is transcribed from a class 1 flagellar promoter. FlhD 2 C 2 , in turn, activates 70 -dependent transcription from the class 2 flagellar promoters that drive expression of the structural subunits required for the hook-basal body structure and expression of regulatory subunits (10, 11). One of these regulatory subunits, 28 or FliA, is encoded by the fliAZ operon. FliA can associate with the core RNA polymerase to drive transcription of the class 3 flagellar genes (12). The activity of FliA depends on its interaction with the cytoplasmic anti-sigma factor FlgM, which inhibits the FliA-RNA polymerase association until completion of the hook-basal bo...

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Section: Discussionmentioning

confidence: 78%

The Flagellar Sigma Factor FliA Regulates Adhesion and Invasion of Crohn Disease-associated Escherichia coli via a Cyclic Dimeric GMP-dependent Pathway

Claret

Miquel

Vieille

et al. 2007

Journal of Biological Chemistry

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“…The crude product (11% cyclization yield) was purified by reversedphase HPLC and characterized by MALDI-TOF MS, as discussed later. Reversed-phase HPLC analyses were carried out on Teknokroma C18 columns (10 m, 250 ϫ 4.6 mm), using a multistep gradient of 0.05 M aq ammonium acetate, pH 7.0, and ACN/H 2O (1:1) at 1 ml/min (12,31). MALDI-TOF MS analysis (Voyager-DERP, Applied Biosystems) was performed in the negative mode using ammonium citrate and either ␣-cyano-hydroxycinnamic acid or trihydroxyacetophenone matrices: m/z 688.…”

Section: Methodsmentioning

confidence: 99%

Genetic reductionist approach for dissecting individual roles of GGDEF proteins within the c-di-GMP signaling network in Salmonella

Solano

García

Latasa

et al. 2009

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

116

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Bacteria have developed an exclusive signal transduction system involving multiple diguanylate cyclase and phosphodiesterase domain-containing proteins (GGDEF and EAL/HD-GYP, respectively) that modulate the levels of the same diffusible molecule, 3 -5 -cyclic diguanylic acid (c-di-GMP), to transmit signals and obtain specific cellular responses. Current knowledge about c-di-GMP signaling has been inferred mainly from the analysis of recombinant bacteria that either lack or overproduce individual members of the pathway, without addressing potential compensatory effects or interferences between them. Here, we dissected c-di-GMP signaling by constructing a Salmonella strain lacking all GGDEF-domain proteins and then producing derivatives, each restoring 1 protein. Our analysis showed that most GGDEF proteins are constitutively expressed and that their expression levels are not interdependent. Complete deletion of genes encoding GGDEFdomain proteins abrogated virulence, motility, long-term survival, and cellulose and fimbriae synthesis. Separate restoration revealed that 4 proteins from Salmonella and 1 from Yersinia pestis exclusively restored cellulose synthesis in a c-di-GMP-dependent manner, indicating that c-di-GMP produced by different GGDEF proteins can activate the same target. However, the restored strain containing the STM4551-encoding gene recovered all other phenotypes by means of gene expression modulation independently of c-di-GMP. Specifically, fimbriae synthesis and virulence were recovered through regulation of csgD and the plasmid-encoded spvAB mRNA levels, respectively. This study provides evidence that the regulation of the GGDEF-domain proteins network occurs at 2 levels: a level that strictly requires c-di-GMP to control enzymatic activities directly, restricted to cellulose synthesis in our experimental conditions, and another that involves gene regulation for which c-di-GMP synthesis can be dispensable.biofilm formation ͉ Salmonella virulence ͉ signal transduction system cellulose ͉ STM4551

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“…A number of studies have concluded that c-di-GMP functions via high specificity based on the observation that the intracellular concentration of c-di-GMP does not directly correlate with phenotypic expression (14)(15)(16)(17), an observation inconsistent with a low-specificity system. These studies relied on mutagenesis of respective DGCs.…”

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confidence: 99%

Quantification of high-specificity cyclic diguanylate signaling

Massie¹,

Reynolds²,

Koestler³

et al. 2012

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

145

143

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Cyclic di-GMP (c-di-GMP) is a second messenger molecule that regulates the transition between sessile and motile lifestyles in bacteria. Bacteria often encode multiple diguanylate cyclase (DGC) and phosphodiesterase (PDE) enzymes that produce and degrade c-di-GMP, respectively. Because of multiple inputs into the c-di-GMP-signaling network, it is unclear whether this system functions via high or low specificity. High-specificity signaling is characterized by individual DGCs or PDEs that are specifically associated with downstream c-di-GMP-mediated responses. In contrast, low-specificity signaling is characterized by DGCs or PDEs that modulate a general signal pool, which, in turn, controls a global c-di-GMPmediated response. To determine whether c-di-GMP functions via high or low specificity in Vibrio cholerae, we correlated the in vivo c-di-GMP concentration generated by seven DGCs, each expressed at eight different levels, to the c-di-GMP-mediated induction of biofilm formation and transcription. There was no correlation between total intracellular c-di-GMP levels and biofilm formation or gene expression when considering all states. However, individual DGCs showed a significant correlation between c-di-GMP production and c-di-GMP-mediated responses. Moreover, the rate of phenotypic change versus c-di-GMP concentration was significantly different between DGCs, suggesting that bacteria can optimize phenotypic output to c-di-GMP levels via expression or activation of specific DGCs. Our results conclusively demonstrate that c-di-GMP does not function via a simple, low-specificity signaling pathway in V. cholerae.signaling specificity | systems biology

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Hierarchical involvement of various GGDEF domain proteins in rdar morphotype development of Salmonella enterica serovar Typhimurium

Cited by 189 publications

References 47 publications

The Flagellar Sigma Factor FliA Regulates Adhesion and Invasion of Crohn Disease-associated Escherichia coli via a Cyclic Dimeric GMP-dependent Pathway

The Flagellar Sigma Factor FliA Regulates Adhesion and Invasion of Crohn Disease-associated Escherichia coli via a Cyclic Dimeric GMP-dependent Pathway

Genetic reductionist approach for dissecting individual roles of GGDEF proteins within the c-di-GMP signaling network in Salmonella

Quantification of high-specificity cyclic diguanylate signaling

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