Cyclic di-GMP-Dependent Signaling Pathways in the Pathogenic Firmicute Listeria monocytogenes

被引：79

作者：

Chen, Li-Hong ^{[1
]}

Koeseoglu, Volkan K. ^{[1
]}

Guevener, Zehra T. ^{[1
]}

Myers-Morales, Tanya ^{[2
]}

Reed, Joseph M. ^{[1
]}

D'Orazio, Sarah E. F. ^{[2
]}

Miller, Kurt W. ^{[1
]}

Gomelsky, Mark ^{[1
]}

机构：

[1] Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA

[2] Univ Kentucky, Dept Microbiol Immunol & Mol Genet, Lexington, KY USA

来源：

PLOS PATHOGENS | 2014年 / 10卷 / 08期

基金：

美国国家科学基金会; 美国国家航空航天局; 美国国家卫生研究院;

关键词：

BIOFILM FORMATION; DOMAIN PROTEIN; ALLOSTERIC CONTROL; SALMONELLA-TYPHIMURIUM; CELLULOSE SYNTHESIS; MOLECULAR-BIOLOGY; PILZ DOMAIN; DIGUANYLATE; CELL; EXOPOLYSACCHARIDE;

D O I：

10.1371/journal.ppat.1004301

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 (Delta pdeB/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.

引用

页数：15

共 97 条

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