Cyclic di-GMP-dependent Signaling Pathways in the Pathogenic Firmicute Listeria monocytogenes
| Autor: | Tanya Myers-Morales, Li-Hong Chen, Joseph M. Reed, Mark Gomelsky, Kurt W. Miller, Volkan K. Köseoğlu, Zehra Tüzün Güvener, Sarah E. F. D'Orazio |
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| Rok vydání: | 2014 |
| Předmět: |
Cyclic di-GMP
QH301-705.5 Diguanylate cyclase activity Immunology medicine.disease_cause Biochemistry Microbiology Mice chemistry.chemical_compound Bacterial Proteins Listeria monocytogenes Virology EAL domain Medicine and Health Sciences Genetics medicine Animals Listeriosis Biology (General) Cyclic GMP Molecular Biology Chromatography High Pressure Liquid Mice Inbred BALB C Virulence biology Escherichia coli Proteins Biofilm Biology and Life Sciences Gene Expression Regulation Bacterial RC581-607 GGDEF domain Cell aggregation 3. Good health Disease Models Animal Infectious Diseases chemistry biology.protein Female Parasitology Diguanylate cyclase Immunologic diseases. Allergy Phosphorus-Oxygen Lyases Research Article Signal Transduction |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 10, Iss 8, p e1004301 (2014) |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1004301 |
| Popis: | 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. Author Summary Listeria monocytogenes is ubiquitously present in the environment, highly adaptable and tolerant to various stresses. L. monocytogenes is also a foodborne pathogen associated with the largest foodborne outbreaks in recent US history. Signaling pathways involving the second messenger c-di-GMP play important roles in increased stress survival of proteobacteria and mycobacteria, yet roles of c-di-GMP signaling pathways in L. monocytogenes have remained unexplored. Here, we identified and systematically characterized functions of the proteins involved in c-di-GMP synthesis, degradation and sensing. We show that elevated c-di-GMP levels in L. monocytogenes result in synthesis of a previously unknown exopolysaccharide that promotes cell aggregation, inhibits motility in semi-solid media, and importantly, enhances bacterial tolerance to commonly used disinfectants as well as desiccation. These properties of the exopolysaccharide may increase listerial survival in food processing plants as well as on produce during transportation and storage. Elevated c-di-GMP levels also grossly diminish listerial invasiveness in enterocytes in vitro, and impair bacterial accumulation in selected mouse organs during oral infection. |
| Databáze: | OpenAIRE |
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