Role of the group B antigen of Streptococcus agalactiae: A peptidoglycan-anchored polysaccharide involved in cell wall biogenesis (original) (raw)
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Staphylococcus and Streptococcus, 2019
Streptococcus agalactiae or Group B streptococcus (GBS) is an opportunistic human pathogen known for their invasive diseases caused in newborns, pregnant women, and nonpregnant adults. This pathogen even being an asymptomatic colonizer of adult humans, still they result in a broad range of disease manifestations starting from mild skin diseases to pneumonia, meningitis, and septicemia. Of the 10 GBS capsular types, the majority of invasive neonatal diseases are associated with the serotype III. GBS is a pathogen that has developed some strategies to resist host immune defenses. The formidable array of GBS virulence factors makes this bacterium at the forefront of neonatal pathogens. The involvement of bacterial components in the host-pathogen interaction of GBS pathogenesis and its related diseases is thought to be due to a variety of virulence factors expressed by Streptococcus agalactiae. Pathogenic factors of streptococcus promote infections by their coordinated activity. These factors/determinants initially get a stimulus by the communication between specific ligands and their respective receptors in a hostpathogen interaction. These in turn activate adhesion and invasion mechanisms by mediating the attachment of pathogen via cell wall associated/secretory proteins, e.g., adhesins followed by their entry into the host cell eventually deciding their fate to live by activation of mechanisms like phagocytosis. These mediators/determinants also modulate the immune responses by the host toward the pathogen. A number of new GBS surface-exposed or secreted proteins have been identified (GBS immunogenic bacterial adhesion protein, leucine-rich repeat of GBS, serinerich repeat proteins), the three-dimensional structures of known streptococcal proteins (αC protein, C5a peptidase) have been solved, and an understanding of the pathogenetic role of "old" and new determinants has been better defined in recent years. Recently, a 39kDa Invasion Inhibitory Factor (IIF) was isolated from GBS playing an important role in its invasion. A homogeneous non-toxic 39 kDa factor from the cytosol of GBS showing a homology with xenobiotic response element type transcriptional regulator protein adds another quill to the GBS protein panama, thus indicating that such protein molecules can be efficiently explored as suitable vaccine candidates. These observations add a novel aspect to bacterial pathogenesis where bacteria's own intracellular protein component can act as a potential therapeutic candidate by decreasing the severity of disease thus promoting its invasion inhibition.
The bifunctional peptidoglycan lysin of Streptococcus agalactiae bacteriophage B30
Microbiology, 2004
A group B streptococcal (GBS) bacteriophage lysin gene was cloned and expressed in Escherichia coli. The purified recombinant enzyme, calculated to have a molecular mass of 49 677 Da, lysed GBS cells. The susceptibility of GBS cells to lysis by the enzyme depended upon the growth stage at which they were harvested, with early exponential phase cells most sensitive. Calcium ions enhanced the activity of the enzyme. The enzyme also lysed other b-haemolytic streptococci, including groups A, C, E and G streptococci, but not common oral streptococci, including Streptococcus mutans. The generation of both reducing activity and N-terminal alanine residues during lysis indicated that the lysin is a bifunctional enzyme, possessing both glycosidase and endopeptidase activities. This is consistent with the presence of two conserved sequence domains, an Acm (acetylmuramidase) domain associated with lysozyme activity, and a CHAP (cysteine, histidine-dependent amidohydrolases/peptidases) domain associated with endopeptidase activity. Site-directed mutagenesis of conserved cysteine and histidine residues in the CHAP domain and conserved aspartate and glutamate residues in the Acm domain confirmed their importance for lysozyme and endopeptidase activity respectively.
Identification of Immunogenic Surface Proteins of Streptococcus agalactiae
The aim of the studies was to identify immunogenic proteins of Streptococcus agalactiae (group B streptococcus; GBS) isolates. Investigation of the immunoreactivity with human sera allowed us to determine major immunogenic proteins which might be potential candidates for the development of vaccine. For the study, we have selected 60 genetically different, well-characterized GBS clinical isolates. The proteins immunoreactivity with 24 human sera from patients with GBS infections, carriers, and control group without GBS was detected by SDS-PAGE and Western blotting. As a result, some major immunogenic proteins were identified, of which four proteins with molecular masses of about 45 to 50 kDa, which exhibited the highest immunoreactivity features, were analyzed by LC-MS/MS. The proteins were identified by comparative analysis of peptides masses using MASCOT and statistical analysis. The results showed known molecules such as enolase (47.4 kDa), aldehyde dehydrogenase (50.6 kDa), and ones not previously described such as trigger factor (47 kDa) and elongation factor Tu (44 kDa). The preliminary results indicated that some GBS proteins that elicit protective immunity hold promise not only as components in a vaccine as antigens but also as carriers or adjuvants in polysaccharide conjugate vaccines, but more studies are needed.
Characterization of the group-specific polysaccharide of group B Streptococcus
Archives of Biochemistry and Biophysics, 1984
The group-specific polysaccharide of the group B Streptococcus was isolated by nitrous acid extraction followed by gel filtration on Sepharose 6B and chromatography on DEAE-Bio-Gel A. It was composed of rhamnose, galactose, N-acetylglucosamine, and glucitol phosphate. Mild periodate oxidation of the polysaccharide resulted in a rapid reduction in molecular weight, indicating that the glucitol was located in the backbone of the polymer. High-resolution 31P NMR showed the presence of a single type of phosphodiester bond in the molecule. Methylation analysis and several specific chemical degradations were done to determine sugar linkages. The basic structure of the group B polysaccharide consists of a backbone of 2-linked rhamnose, 2,4-linked rhamnose, and glucitol phosphate, and side chains of rhamnose(1 -3)galactose(l -3)N-acetylglucosamine linked to the 4-position of a rhamnose in the backbone. o
PplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides
2021
The cell wall of the human bacterial pathogen Group A Streptococcus (GAS) consists of peptidoglycan decorated with the Lancefield group A carbohydrate (GAC). GAC is a promising target for the development of GAS vaccines. In this study, employing chemical, compositional, and NMR methods, we show that GAC is attached to peptidoglycan via glucosamine 1-phosphate. This structural feature makes the GAC-peptidoglycan linkage highly sensitive to cleavage by nitrous acid and resistant to mild acid conditions. Using this characteristic of the GAS cell wall, we identify PplD as a protein required for deacetylation of linkage N-acetylglucosamine (GlcNAc). X-ray structural analysis indicates that PplD performs catalysis via a modified acid/base mechanism. Genetic surveys in silico together with functional analysis indicate that PplD homologs deacetylate the polysaccharide linkage in many streptococcal species. We further demonstrate that introduction of positive charges to the cell wall by GlcN...
Analysis of the Streptococcus agalactiae exoproteome
The two-component regulatory system CovRS is the main regulator of virulence gene expression in Group B Streptococcus (GBS), the leading cause of invasive infections in neonates. In this study we analyzed by mass spectrometry the GBS extracellular protein complex (i.e. the exoproteome) of NEM316 wild-type (WT) strain and its isogenic covRS deletion mutant (ΔcovRS). A total of 53 proteins, 49 of which had classical secretion signals, were identified: 12 were released by both strains while 21 and 20 were released exclusively by WT and ΔcovRS strains, respectively. In addition to known surface proteins, we detected here unstudied cell-wall associated proteins and/or orthologs of putative virulence factors present in other pathogenic streptococci. While the functional role of these proteins remains to be elucidated, our data suggest that the analysis of the exoproteome of bacterial pathogens under different gene expression conditions may be a powerful tool for the rapid identification of novel virulence factors and vaccine candidates.