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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

Domain Architecture and Genome Structure(A) CR1 to CR4, found through multiple alignments, are represented by rectangles ranging from light blue (CR1) to dark blue (CR4). Other motifs are represented as follows: predicted signal peptides as magenta rectangles, transmembrane regions as orange rectangles, Lin-12/Notch repeats as red pentagons, and EF-hands as green circles.(B) The genome structure of the human and fly Stealth homologs is represented, with the exons depicted as green rectangles separated by introns of indicated size.(C) Two splice variants lead to different N-terminal sequences, as supported by mouse EST sequences. Splicing reconstructs a codon for tyrosine (Y). Both proteins contain a predicted signal peptide.
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pcbi-0010063-g002: Domain Architecture and Genome Structure(A) CR1 to CR4, found through multiple alignments, are represented by rectangles ranging from light blue (CR1) to dark blue (CR4). Other motifs are represented as follows: predicted signal peptides as magenta rectangles, transmembrane regions as orange rectangles, Lin-12/Notch repeats as red pentagons, and EF-hands as green circles.(B) The genome structure of the human and fly Stealth homologs is represented, with the exons depicted as green rectangles separated by introns of indicated size.(C) Two splice variants lead to different N-terminal sequences, as supported by mouse EST sequences. Splicing reconstructs a codon for tyrosine (Y). Both proteins contain a predicted signal peptide.

Mentions: Stealth proteins are characterized by four conserved regions (CRs) referred to as CR1 to CR4 (Figure 1). The N-terminal CR1 consists of a short but strongly conserved sequence motif, IDVVYTF or very similar. The second region, CR2, is approximately 100 residues long and constitutes the most conserved part of this protein family. A standard BLAST search [18] with any CR2 domain identifies all other members of the Stealth family in the current database with highly significant E-values. CR3 is about 50 residues long but less well conserved. Finally, the C-terminal CR4 includes an almost universally conserved tetrapetide, CLND or CIND. Adjacent and between these domains are divergent sequence regions of variable length that may contain additional domains (Figures 1 and 2A).


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)

Domain Architecture and Genome Structure(A) CR1 to CR4, found through multiple alignments, are represented by rectangles ranging from light blue (CR1) to dark blue (CR4). Other motifs are represented as follows: predicted signal peptides as magenta rectangles, transmembrane regions as orange rectangles, Lin-12/Notch repeats as red pentagons, and EF-hands as green circles.(B) The genome structure of the human and fly Stealth homologs is represented, with the exons depicted as green rectangles separated by introns of indicated size.(C) Two splice variants lead to different N-terminal sequences, as supported by mouse EST sequences. Splicing reconstructs a codon for tyrosine (Y). Both proteins contain a predicted signal peptide.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-0010063-g002: Domain Architecture and Genome Structure(A) CR1 to CR4, found through multiple alignments, are represented by rectangles ranging from light blue (CR1) to dark blue (CR4). Other motifs are represented as follows: predicted signal peptides as magenta rectangles, transmembrane regions as orange rectangles, Lin-12/Notch repeats as red pentagons, and EF-hands as green circles.(B) The genome structure of the human and fly Stealth homologs is represented, with the exons depicted as green rectangles separated by introns of indicated size.(C) Two splice variants lead to different N-terminal sequences, as supported by mouse EST sequences. Splicing reconstructs a codon for tyrosine (Y). Both proteins contain a predicted signal peptide.
Mentions: Stealth proteins are characterized by four conserved regions (CRs) referred to as CR1 to CR4 (Figure 1). The N-terminal CR1 consists of a short but strongly conserved sequence motif, IDVVYTF or very similar. The second region, CR2, is approximately 100 residues long and constitutes the most conserved part of this protein family. A standard BLAST search [18] with any CR2 domain identifies all other members of the Stealth family in the current database with highly significant E-values. CR3 is about 50 residues long but less well conserved. Finally, the C-terminal CR4 includes an almost universally conserved tetrapetide, CLND or CIND. Adjacent and between these domains are divergent sequence regions of variable length that may contain additional domains (Figures 1 and 2A).

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