Limits...
Cyclic di-GMP-dependent signaling pathways in the pathogenic Firmicute Listeria monocytogenes.

Chen LH, Köseoğlu VK, Güvener ZT, Myers-Morales T, Reed JM, D'Orazio SE, Miller KW, Gomelsky M - PLoS Pathog. (2014)

Bottom Line: The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis.The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces.The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, University of Wyoming, Laramie, Wyoming, United States of America.

ABSTRACT
We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase genes (ΔpdeB/C/D) or expression of a heterologous diguanylate cyclase stimulated production of a previously unknown exopolysaccharide. The synthesis of this exopolysaccharide was attributed to the pssA-E (lmo0527-0531) gene cluster. The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis. The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces. The exopolysaccharide also greatly enhances bacterial tolerance to commonly used disinfectants as well as desiccation, which may contribute to survival of L. monocytogenes on contaminated food products and in food-processing facilities. The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence.

Show MeSH

Related in: MedlinePlus

In silico analysis of genes and proteins involved in c-di-GMP signaling in L. monocytogenes.Depicted are genes predicted to encode DGCs (DgcA-C), c-di-GMP PDEs (PdeB-D), a c-di-GMP receptor (PssE), and listerial EPS biosynthesis machinery. Protein domain architectures are taken from the Pfam database: 5TM, a conserved five-transmembrane module; unmarked red box, transmembrane domain; crossed GGDEF domain, enzymatically inactive GGDEF domain.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4125290&req=5

ppat-1004301-g001: In silico analysis of genes and proteins involved in c-di-GMP signaling in L. monocytogenes.Depicted are genes predicted to encode DGCs (DgcA-C), c-di-GMP PDEs (PdeB-D), a c-di-GMP receptor (PssE), and listerial EPS biosynthesis machinery. Protein domain architectures are taken from the Pfam database: 5TM, a conserved five-transmembrane module; unmarked red box, transmembrane domain; crossed GGDEF domain, enzymatically inactive GGDEF domain.

Mentions: C-di-GMP is synthesized by diguanylate cyclases (DGCs), which contain GGDEF domains [36], [37], and degraded by c-di-GMP-specific phosphodiesterases (PDEs), which contain either EAL [38]–[40] or HD-GYP [41] catalytic domains. The currently sequenced strains of L. monocytogenes, and the majority of related listerial species encode four GGDEF domain proteins, three EAL domain proteins and no HD-GYP domain proteins (Pfam database [42]) (Fig. 1).


Cyclic di-GMP-dependent signaling pathways in the pathogenic Firmicute Listeria monocytogenes.

Chen LH, Köseoğlu VK, Güvener ZT, Myers-Morales T, Reed JM, D'Orazio SE, Miller KW, Gomelsky M - PLoS Pathog. (2014)

In silico analysis of genes and proteins involved in c-di-GMP signaling in L. monocytogenes.Depicted are genes predicted to encode DGCs (DgcA-C), c-di-GMP PDEs (PdeB-D), a c-di-GMP receptor (PssE), and listerial EPS biosynthesis machinery. Protein domain architectures are taken from the Pfam database: 5TM, a conserved five-transmembrane module; unmarked red box, transmembrane domain; crossed GGDEF domain, enzymatically inactive GGDEF domain.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125290&req=5

ppat-1004301-g001: In silico analysis of genes and proteins involved in c-di-GMP signaling in L. monocytogenes.Depicted are genes predicted to encode DGCs (DgcA-C), c-di-GMP PDEs (PdeB-D), a c-di-GMP receptor (PssE), and listerial EPS biosynthesis machinery. Protein domain architectures are taken from the Pfam database: 5TM, a conserved five-transmembrane module; unmarked red box, transmembrane domain; crossed GGDEF domain, enzymatically inactive GGDEF domain.
Mentions: C-di-GMP is synthesized by diguanylate cyclases (DGCs), which contain GGDEF domains [36], [37], and degraded by c-di-GMP-specific phosphodiesterases (PDEs), which contain either EAL [38]–[40] or HD-GYP [41] catalytic domains. The currently sequenced strains of L. monocytogenes, and the majority of related listerial species encode four GGDEF domain proteins, three EAL domain proteins and no HD-GYP domain proteins (Pfam database [42]) (Fig. 1).

Bottom Line: The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis.The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces.The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, University of Wyoming, Laramie, Wyoming, United States of America.

ABSTRACT
We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase genes (ΔpdeB/C/D) or expression of a heterologous diguanylate cyclase stimulated production of a previously unknown exopolysaccharide. The synthesis of this exopolysaccharide was attributed to the pssA-E (lmo0527-0531) gene cluster. The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis. The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces. The exopolysaccharide also greatly enhances bacterial tolerance to commonly used disinfectants as well as desiccation, which may contribute to survival of L. monocytogenes on contaminated food products and in food-processing facilities. The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence.

Show MeSH
Related in: MedlinePlus