Dataset Information

Dentipain, a Streptococcus pyogenes IdeS protease homolog, is a novel virulence factor of Treponema denticola.

ABSTRACT: Treponema denticola is a major pathogen of chronic periodontitis. Analysis of the T. denticola genome revealed a gene orthologous with a cysteine protease-encoding gene from Streptococcus pyogenes (IdeS). IdeS interferes with IgG-dependent opsonophagocytosis by specific cleavage of IgG molecules. Analysis of this gene (termed ideT) revealed it to encode a two-domain protein whose N-terminus is composed of tandem immunoglobulin-like domains followed by a C-terminal IdeS-like protease domain. In this study we show that during secretion the IdeT protein is processed into an N-terminal fragment which remains associated with the cell, and a C-terminal part released into the medium. Although the secreted domain of IdeT, termed dentipain, shows only 25% identity to the IdeS protease, the putative catalytic cysteine and histidine residues are strongly conserved. Recombinant dentipain cleaves the insulin ?-chain, an activity which is inhibited by E-64, a diagnostic inhibitor of cysteine proteases. Apart from insulin no cleavage of other protein substrates was detected, suggesting that dentipain has oligopeptidase activity. A mutant strain was constructed expressing a modified IdeT variant, the dentipain domain of which was deleted. This strain was found to be significantly reduced in its abscess-forming activity compared with the parental strain in a murine abscess model, suggesting that dentipain contributes to the virulence of T. denticola.

SUBMITTER: Ishihara K

PROVIDER: S-EPMC3153314 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dentipain, a Streptococcus pyogenes IdeS protease homolog, is a novel virulence factor of Treponema denticola.

Ishihara Kazuyuki K Wawrzonek Katarzyna K Shaw Lindesey N LN Inagaki Satoru S Miyamoto Meguru M Potempa Jan J

Biological chemistry 20100901 9

Treponema denticola is a major pathogen of chronic periodontitis. Analysis of the T. denticola genome revealed a gene orthologous with a cysteine protease-encoding gene from Streptococcus pyogenes (IdeS). IdeS interferes with IgG-dependent opsonophagocytosis by specific cleavage of IgG molecules. Analysis of this gene (termed ideT) revealed it to encode a two-domain protein whose N-terminus is composed of tandem immunoglobulin-like domains followed by a C-terminal IdeS-like protease domain. In t ...[more]

PMID: 20635859

Similar Datasets

Project description:The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds.Group A Streptococcus (GAS) causes human infections ranging from strep throat to life-threatening conditions such as flesh-eating disease and toxic shock syndrome. Common disease-associated clones of GAS can cause both mild and severe infections because of a characteristic mutation and subsequent change in the expression of several genes that develops under host immune selection. One of these genes encodes Mac/IdeS, a protease that has been shown to cleave antibodies important to the immune defense system. In this study, we found that while Mac/IdeS is highly expressed in hypervirulent GAS, it does not significantly contribute to the ability of the bacteria to survive white blood cell killing or produce invasive infection in the mouse. These data underscore the importance of correlating studies on virulence factor function with physiologic expression levels and the complexity of streptococcal pathogenesis and contribute to our overall understanding of how GAS causes disease.

Dataset Information

Dentipain, a Streptococcus pyogenes IdeS protease homolog, is a novel virulence factor of Treponema denticola.

Publications

Dentipain, a Streptococcus pyogenes IdeS protease homolog, is a novel virulence factor of Treponema denticola.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets