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In silico analysis of a family of extracellular polysaccharide deacetylases involved in virulence of pathogenic gram-positive cocci
© Aziz; licensee BioMed Central Ltd. 2010
- Published: 23 July 2010
- Multiple Sequence Alignment
- Streptococcus Pneumoniae
- Functional Homolog
- Human Lysozyme
Pathogenic bacteria incessantly evolve mechanisms to resist their host’s innate immunity. One such mechanism is molecular camouflage: the modification of bacterial surface molecules to make them unrecognizable by the host’s immune system or resistant to its effector molecules. Recently, a peptidoglycan deacetylase (PgdA) was discovered in Streptococcus pneumoniae that renders bacterial peptidoglycan resistant to human lysozyme, thus preventing host-mediated cell wall damage[1–3]. In addition, polysaccharide deacetylases with different substrate specificities were identified in other gram-positive bacteria and shown to contribute to virulence (e.g., IcaB of Staphylococcus epidermidis  and Pdi or Streptococcus iniae ).
In this study, genomes of streptococci and other representative gram-positive cocci were screened for the presence of functional homologs of PgdA, the prototypic pneumococcal peptidoglycan deacetylase. Subsequently, amino acid sequences of homologous proteins were aligned and mapped to the three-dimensional structure of PgdA (Protein Data Bank ID: 2c1g). The ConSurf tool[7, 8] was used for surface mapping of the phylogenetic information calculated from the multiple sequence alignments.
Taken together, these data suggest the conservation of PgdA in pathogenic streptococci, the presence of PgdA orthologs and paralogs in gram-positive cocci, and the high conservation of amino acid residues surrounding the active site of these enzymes. These residues may be tested as potential targets for the rational design of novel, immune-assisted antibacterial agents.
- Vollmer W, Tomasz A: The pgdA gene encodes for a peptidoglycan N-acetylglucosamine deacetylase in Streptococcus pneumoniae. J Biol Chem 2000, 275: 20496–20501. 10.1074/jbc.M910189199View ArticlePubMedGoogle Scholar
- Vollmer W, Tomasz A: Peptidoglycan N-acetylglucosamine deacetylase, a putative virulence factor in Streptococcus pneumoniae. Infect Immun 2002, 70: 7176–7178. 10.1128/IAI.70.12.7176-7178.2002PubMed CentralView ArticlePubMedGoogle Scholar
- Blair DE, Schuttelkopf AW, MacRae JI, van Aalten DM: Structure and metal-dependent mechanism of peptidoglycan deacetylase, a streptococcal virulence factor. Proc Natl Acad Sci USA 2005, 102: 15429–15434. 10.1073/pnas.0504339102PubMed CentralView ArticlePubMedGoogle Scholar
- Vuong C, Kocianova S, Voyich JM, Yao Y, Fischer ER, DeLeo FR, Otto M: A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence. J Biol Chem 2004, 279: 54881–54886. 10.1074/jbc.M411374200View ArticlePubMedGoogle Scholar
- Milani CJ, Aziz RK, Locke JB, Dahesh S, Nizet V, Buchanan JT: The novel polysaccharide deacetylase homologue Pdi contributes to virulence of the aquatic pathogen Streptococcus iniae. Microbiology 2010, 156: 543–554. 10.1099/mic.0.028365-0PubMed CentralView ArticlePubMedGoogle Scholar
- Thompson JD, Higgins DG, Gibson TJ: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994, 22: 4673–4680. 10.1093/nar/22.22.4673PubMed CentralView ArticlePubMedGoogle Scholar
- Glaser F, Pupko T, Paz I, Bell RE, Bechor-Shental D, Martz E, Ben-Tal N: ConSurf: identification of functional regions in proteins by surface-mapping of phylogenetic information. Bioinformatics 2003, 19: 163–164. 10.1093/bioinformatics/19.1.163View ArticlePubMedGoogle Scholar
- Landau M, Mayrose I, Rosenberg Y, Glaser F, Martz E, Pupko T, Ben-Tal N: ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res 2005, 33: W299–302. 10.1093/nar/gki370PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd.