Phenotypic Convergence Mediated by GGDEF-Domain-Containing Proteins

Simm, Roger; Fetherston, Jacqueline D.; Kader, Abdul; Römling, Ute; Perry, Robert D.

doi:10.1128/jb.187.19.6816-6823.2005

Cited by 75 publications

(66 citation statements)

References 47 publications

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“…HmsT and HmsP are hypothesized to control Hms-dependent ECM biosynthesis via their opposing c-di-GMP forming and degrading activities. In keeping with this regulatory scheme, copy number of hmsT is directly related to c-di-GMP levels and biofilm thickness in Y. pestis; conversely, deletion of hmsT or disruption of its GGDEFencoding region result in poor biofilm formation Simm et al 2005). As also predicted by the model, elimination of HmsP or its EAL domain result in thicker biofilm ).…”

Section: Regulation Of Hms-dependent Biofilm Formationmentioning

confidence: 62%

“…hmsT and hmsP, two recently identified chromosomal genes that are unlinked to the hmsHFRS locus and to each other, encode a GGDEF-domain protein with c-di-GMP synthesizing diguanylate cyclase activity and an EAL-domain protein with phosphodiesterase activity, respectively (Bobrov et al 2005;Hare and McDonough 1999;Jones et al 1999;Simm et al 2005). HmsT and HmsP are hypothesized to control Hms-dependent ECM biosynthesis via their opposing c-di-GMP forming and degrading activities.…”

Section: Regulation Of Hms-dependent Biofilm Formationmentioning

confidence: 99%

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Yersinia pestis Biofilm in the Flea Vector and Its Role in the Transmission of Plague

Hinnebusch¹,

Erickson²

2008

Current Topics in Microbiology and Immunology

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Transmission by fleabite is a relatively recent evolutionary adaptation of Yersinia pestis, the bacterial agent of bubonic plague. To produce a transmissible infection, Y. pestis grows as an attached biofilm in the foregut of the flea vector. Biofilm formation both in the flea foregut and in vitro is dependent on an extracellular matrix (ECM) synthesized by the Yersinia hms gene products. The hms genes are similar to the pga and ica genes of Escherichia coli and Staphylococcus epidermidis, respectively, that act to synthesize a poly-β-1,6-N-acetyl-dglucosamine ECM required for biofilm formation. As with extracellular polysaccharide production in many other bacteria, synthesis of the Hms-dependent ECM is controlled by intracellular levels of cyclic-di-GMP. Yersinia pseudotuberculosis, the food-and water-borne enteric pathogen from which Y. pestis evolved recently, possesses identical hms genes and can form biofilm in vitro but not in the flea. The genetic changes in Y. pestis that resulted in adapting biofilm-forming capability to the flea gut environment, a critical step in the evolution of vector-borne transmission, have yet to be identified. During a flea bite, Y. pestis is regurgitated into the dermis in a unique biofilm phenotype, and this has implications for the initial interaction with the mammalian innate immune response.

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Section: Regulation Of Hms-dependent Biofilm Formationmentioning

confidence: 62%

Section: Regulation Of Hms-dependent Biofilm Formationmentioning

confidence: 99%

Yersinia pestis Biofilm in the Flea Vector and Its Role in the Transmission of Plague

Hinnebusch¹,

Erickson²

2008

Current Topics in Microbiology and Immunology

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“…S5). Both genes were selected because their products have been demonstrated to possess DGC activity at 28°C (12,32). Results indicated that ⌬XIIϩP 4551 adrA and ⌬XIIϩP 4551 hmsT exclusively recovered the capacity to synthesize cellulose in a process strictly dependent on DGC activity, because ⌬XIIϩP 4551 adrA and ⌬XIIϩP 4551 hmsT strains containing a degenerate GGGSF motif lost their capacity to activate cellulose synthesis.…”

Section: Consequences Of Removing All Ggdef-domain Proteins In a Singlementioning

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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“…HmsP, a negative regulator of biofilm formation, is an EAL phosphodiesterase and likely degrades c-di-GMP. Like other glycosyltransferases involved in EPS or cellulose productions, the enzymic activity of HmsR may depend upon c-di-GMP (Bobrov et al, 2005;Hare & McDonough, 1999;Jones et al, 1999;Kirillina et al, 2004;Perry et al, 2004;Simm et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Identification of critical amino acid residues in the plague biofilm Hms proteins

et al. 2006

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Yersinia pestis biofilm formation causes massive adsorption of haemin or Congo red in vitro as well as colonization and eventual blockage of the flea proventriculus in vivo. This blockage allows effective transmission of plague from some fleas, like the oriental rat flea, to mammals. Four Hms proteins, HmsH, HmsF, HmsR and HmsS, are essential for biofilm formation, with HmsT and HmsP acting as positive and negative regulators, respectively. HmsH has a β-barrel structure with a large periplasmic domain while HmsF possesses polysaccharide deacetylase and COG1649 domains. HmsR is a putative glycosyltransferase while HmsS has no recognized domains. In this study, specific amino acids within conserved domains or within regions of high similarity in HmsH, HmsF, HmsR and HmsS proteins were selected for site-directed mutagenesis. Some but not all of the substitutions in HmsS and within the periplasmic domain of HmsH were critical for protein function. Substitutions within the glycosyltransferase domain of HmsR and the deacetylase domain of HmsF abolished biofilm formation in Y. pestis. Surprisingly, substitution of highly conserved residues within COG1649 did not affect HmsF function.

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Phenotypic Convergence Mediated by GGDEF-Domain-Containing Proteins

Cited by 75 publications

References 47 publications

Yersinia pestis Biofilm in the Flea Vector and Its Role in the Transmission of Plague

Yersinia pestis Biofilm in the Flea Vector and Its Role in the Transmission of Plague

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

Identification of critical amino acid residues in the plague biofilm Hms proteins

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