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In Silico Investigation for Evaluation of the Potential of the SclA Protein in Streptococcus pyogenes.

ABSTRACT: BACKGROUND:Streptococcus pyogenes is an important pathogen that is associated with a range of infections in humans, and causes common and severe invasive diseases. Currently, antimicrobial therapy is the first choice for the treatment of S. pyogenes; however, the emergence of antimicrobial resistance and side effects of antibacterial drugs is increasing. Consequently, there is an increased demand for novel drug targets and vaccine design. OBJECTIVES:To develop an effective vaccine against Streptococcus pyogenes (group A streptococcus) , we described a novel collagen-like surface protein of S. pyogenes which is important virulence factors. MATERIALS AND METHODS:In this study, we focused on the SclA protein of S. pyogenes and characterized it using bioinformatic tools to introduce it as a candidate novel drug as a candidate for use in vaccine design. The secondary structure was determined and the 3D structure was modeled using SWISS-MODEL workspace. The immune epitope database analysis (IEDB) resource was used to predict regions of SclA that are likely to be recognized as epitopes. RESULTS:The SclA protein is present on the cell surface of the cell and has interact with a common ligand by its hypervariable NH2-terminal regions. The IEDB showed that the maximum peptide length that is likely to be predicted as an epitope is of 6 amino acids, from amino acid 26 to 31, with a score of 4.791. This epitope can be considered for use in Antibody and drug design. CONCLUSIONS:Data from this study about SclA were not sufficient and further studies are needed; however, the information here suggests that SclA could be a candidate for further research on the design of drugs and vaccines against S. pyogenes infections.

SUBMITTER: Pourhajibagher M

PROVIDER: S-EPMC4609172 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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In Silico Investigation for Evaluation of the Potential of the SclA Protein in Streptococcus pyogenes.

Pourhajibagher Maryam M Bahador Abbas A

Jundishapur journal of microbiology 20150909 9

<h4>Background</h4>Streptococcus pyogenes is an important pathogen that is associated with a range of infections in humans, and causes common and severe invasive diseases. Currently, antimicrobial therapy is the first choice for the treatment of S. pyogenes; however, the emergence of antimicrobial resistance and side effects of antibacterial drugs is increasing. Consequently, there is an increased demand for novel drug targets and vaccine design.<h4>Objectives</h4>To develop an effective vaccine ...[more]

PMID: 26495104

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Project description:The enzymatic hydrolysis of alpha-mannosides is catalyzed by glycoside hydrolases (GH), termed alpha-mannosidases. These enzymes are found in different GH sequence-based families. Considerable research has probed the role of higher eukaryotic "GH38" alpha-mannosides that play a key role in the modification and diversification of hybrid N-glycans; processes with strong cellular links to cancer and autoimmune disease. The most extensively studied of these enzymes is the Drosophila GH38 alpha-mannosidase II, which has been shown to be a retaining alpha-mannosidase that targets both alpha-1,3 and alpha-1,6 mannosyl linkages, an activity that enables the enzyme to process GlcNAc(Man)(5)(GlcNAc)(2) hybrid N-glycans to GlcNAc(Man)(3)(GlcNAc)(2). Far less well understood is the observation that many bacterial species, predominantly but not exclusively pathogens and symbionts, also possess putative GH38 alpha-mannosidases whose activity and specificity is unknown.Here we show that the Streptococcus pyogenes (M1 GAS SF370) GH38 enzyme (Spy1604; hereafter SpGH38) is an alpha-mannosidase with specificity for alpha-1,3 mannosidic linkages. The 3D X-ray structure of SpGH38, obtained in native form at 1.9 A resolution and in complex with the inhibitor swainsonine (K(i) 18 microM) at 2.6 A, reveals a canonical GH38 five-domain structure in which the catalytic "-1" subsite shows high similarity with the Drosophila enzyme, including the catalytic Zn(2+) ion. In contrast, the "leaving group" subsites of SpGH38 display considerable differences to the higher eukaryotic GH38s; features that contribute to their apparent specificity.Although the in vivo function of this streptococcal GH38 alpha-mannosidase remains unknown, it is shown to be an alpha-mannosidase active on N-glycans. SpGH38 lies on an operon that also contains the GH84 hexosaminidase (Spy1600) and an additional putative glycosidase. The activity of SpGH38, together with its genomic context, strongly hints at a function in the degradation of host N- or possibly O-glycans. The absence of any classical signal peptide further suggests that SpGH38 may be intracellular, perhaps functioning in the subsequent degradation of extracellular host glycans following their initial digestion by secreted glycosidases.

Project description:Bacteria respond to environmental changes through the co-ordinated regulation of gene expression, often mediated by two-component regulatory systems (TCS). Group A Streptococcus (GAS), a bacterium which infects multiple human body sites and causes multiple diseases, possesses up to 14 TCS. In this study we examined genetic variation in the coding sequences and non-coding DNA upstream of these TCS as a method for evaluating relationships between different GAS emm-types, and potential associations with GAS disease. Twelve of the 14 TCS were present in 90% of the genomes examined. The length of the intergenic regions (IGRs) upstream of TCS coding regions varied from 39 to 345 nucleotides, with an average nucleotide diversity of 0.0064. Overall, IGR allelic variation was generally conserved with an emm-type. Subsequent phylogenetic analysis of concatenated sequences based on all TCS IGR sequences grouped genomes of the same emm-type together. However grouping with emm-pattern and emm-cluster-types was much weaker, suggesting epidemiological and functional properties associated with the latter are not due to evolutionary relatedness of emm-types. All emm5, emm6 and most of the emm18 genomes, all historically considered rheumatogenic emm-types clustered together, suggesting a shared evolutionary history. However emm1, emm3 and several emm18 genomes did not cluster within this group. These latter emm18 isolates were epidemiologically distinct from other emm18 genomes in study, providing evidence for local variation. emm-types associated with invasive disease or nephritogenicity also did not cluster together. Considering the TCS coding sequences (cds), correlation with emm-type was weaker than for the IGRs, and no strong correlation with disease was observed. Deletion of the malate transporter, maeP, was identified that serves as a putative marker for the emm89.0 subtype, which has been implicated in invasive outbreaks. A recombination-related, subclade-forming DNA motif was identified in the putative receiver domain of the Spy1556 response regulator that correlated with throat-associated emm-pattern-type A-C strains.

Dataset Information

In Silico Investigation for Evaluation of the Potential of the SclA Protein in Streptococcus pyogenes.

Publications

In Silico Investigation for Evaluation of the Potential of the SclA Protein in Streptococcus pyogenes.

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