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Stealth proteins: in silico identification of a novel protein family rendering bacterial pathogens invisible to host immune defense.

Sperisen P, Schmid CD, Bucher P, Zilian O - PLoS Comput. Biol. (2005)

Bottom Line: Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system.Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system.Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence.

View Article: PubMed Central - PubMed

Affiliation: Swiss Institute of Bioinformatics, Epalinges, Switzerland.

ABSTRACT
There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC) is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.

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Related in: MedlinePlus

Phylogenetic TreeTrees were calculated from amino acid sequence alignments of the four CRs. As in Figure 1, sequences are identified by a species code (see Table 1), protein name (from literature as proposed in this paper), and database accession number, and are color-coded. Dissimilarities are represented by the length of the branches (all with posterior probabilities above 0.95).
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pcbi-0010063-g003: Phylogenetic TreeTrees were calculated from amino acid sequence alignments of the four CRs. As in Figure 1, sequences are identified by a species code (see Table 1), protein name (from literature as proposed in this paper), and database accession number, and are color-coded. Dissimilarities are represented by the length of the branches (all with posterior probabilities above 0.95).

Mentions: The peculiar taxonomic distribution of Stealth (Figure 3) could be the outcome of two different evolutionary scenarios: (i) differential loss of an ancient protein already present in an ancestral form of life, or (ii) horizontal gene transfer between eukaryotes and eubacteria. The second hypothesis appears to be the more plausible, but the direction of the transfer is more difficult to assess. Overall, the protein tree largely follows species phylogeny, at least with regard to the higher level taxonomic groups. This indicates that transfer between eukaryotes and prokaryotes must have been an ancient event. However, several observations suggest that Stealth proteins continue to be horizontally transferred within and between certain bacterial groups. In Gram-negative bacteria, Stealth is inserted into group II capsule operons, which exhibit strong sequence similarity across many species, thus facilitating horizontal gene transfer via homologous recombination [49,50]. Moreover, certain Stealth genes have significantly lower G+C content than the remaining part of the genome [19,21,24,51], which is indicative of a recent acquisition from another species, and some of these genes are flanked by recombination-promoting IS insertion elements or residual fragments thereof [21,24].


Stealth proteins: in silico identification of a novel protein family rendering bacterial pathogens invisible to host immune defense.

Sperisen P, Schmid CD, Bucher P, Zilian O - PLoS Comput. Biol. (2005)

Phylogenetic TreeTrees were calculated from amino acid sequence alignments of the four CRs. As in Figure 1, sequences are identified by a species code (see Table 1), protein name (from literature as proposed in this paper), and database accession number, and are color-coded. Dissimilarities are represented by the length of the branches (all with posterior probabilities above 0.95).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1285062&req=5

pcbi-0010063-g003: Phylogenetic TreeTrees were calculated from amino acid sequence alignments of the four CRs. As in Figure 1, sequences are identified by a species code (see Table 1), protein name (from literature as proposed in this paper), and database accession number, and are color-coded. Dissimilarities are represented by the length of the branches (all with posterior probabilities above 0.95).
Mentions: The peculiar taxonomic distribution of Stealth (Figure 3) could be the outcome of two different evolutionary scenarios: (i) differential loss of an ancient protein already present in an ancestral form of life, or (ii) horizontal gene transfer between eukaryotes and eubacteria. The second hypothesis appears to be the more plausible, but the direction of the transfer is more difficult to assess. Overall, the protein tree largely follows species phylogeny, at least with regard to the higher level taxonomic groups. This indicates that transfer between eukaryotes and prokaryotes must have been an ancient event. However, several observations suggest that Stealth proteins continue to be horizontally transferred within and between certain bacterial groups. In Gram-negative bacteria, Stealth is inserted into group II capsule operons, which exhibit strong sequence similarity across many species, thus facilitating horizontal gene transfer via homologous recombination [49,50]. Moreover, certain Stealth genes have significantly lower G+C content than the remaining part of the genome [19,21,24,51], which is indicative of a recent acquisition from another species, and some of these genes are flanked by recombination-promoting IS insertion elements or residual fragments thereof [21,24].

Bottom Line: Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system.Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system.Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence.

View Article: PubMed Central - PubMed

Affiliation: Swiss Institute of Bioinformatics, Epalinges, Switzerland.

ABSTRACT
There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC) is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.

Show MeSH
Related in: MedlinePlus