Antigenic Determinants of Alpha-Like Proteins of
            <i>Streptococcus agalactiae</i>

Mæland, Johan A.; Bevanger, Lars; Lyng, Randi Valsø

doi:10.1128/cdli.11.6.1035-1039.2004

Cited by 13 publications

(37 citation statements)

References 25 publications

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“…Furthermore, smaller amounts of antibodies against alpha and Rib proteins, present in the host, have also been reported to be associated with a higher incidence of disease (67). Therefore, alpha-like proteins have been considered potential antigens for the development of a vaccine against GBS (67)(68)(69). Here, we observed a 4-fold increase in the expression of the rib gene following incubation in whole human blood, leading to a high level of expression of this immunogenic protein.…”

Section: Discussionmentioning

confidence: 63%

Whole-Genome Comparison Uncovers Genomic Mutations between Group B Streptococci Sampled from Infected Newborns and Their Mothers

Almeida¹,

Villain

Joubrel

et al. 2015

J Bacteriol

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Streptococcus agalactiae (group B Streptococcus or GBS), a commensal of the human gut and genitourinary tract, is a leading cause of neonatal infections, in which vertical transmission from mother to child remains the most frequent route of contamination. Here, we investigated whether the progression of GBS from carriage to disease is associated with genomic adaptation. Whole-genome comparison of 47 GBS samples from 19 mother-child pairs uncovered 21 single nucleotide polymorphisms (SNPs) and seven insertions/deletions. Of the SNPs detected, 16 appear to have been fixed in the population sampled whereas five mutations were found to be polymorphic. In the infant strains, 14 mutations were detected, including two independently fixed variants affecting the covRS locus, which is known to encode a major regulatory system of virulence. A one-nucleotide insertion was also identified in the promoter region of the highly immunogenic surface protein Rib gene. Gene expression analysis after incubation in human blood showed that these mutations influenced the expression of virulence-associated genes. Additional identification of three mutated strains in the mothers' milk raised the possibility of the newborns also being a source of contamination for their mothers. Overall, our work showed that GBS strains in carriage and disease scenarios might undergo adaptive changes following colonization. The types and locations of the mutations found, together with the experimental results showing their phenotypic impact, suggest that those in a context of infection were positively selected during the transition of GBS from commensal to pathogen, contributing to an increased capacity to cause disease. IMPORTANCEGroup B Streptococcus (GBS) is a major pathogen responsible for neonatal infections. Considering that its colonization of healthy adults is mostly asymptomatic, the mechanisms behind its switch from a commensal to an invasive state are largely unknown. In this work, we compared the genomic profile of GBS samples causing infections in newborns with that of the GBS colonizing their mothers. Multiple mutations were detected, namely, within key virulence factors, including the response regulator CovR and surface protein Rib, potentially affecting the pathogenesis of GBS. Their overall impact was supported by differences in the expression of virulence-associated genes in human blood. Our results suggest that during GBS's progression to disease, particular variants are positively selected, contributing to the ability of this bacterium to infect its host. Streptococcus agalactiae, or group B Streptococcus (GBS), is currently regarded as one of the leading causes of neonatal sepsis and meningitis worldwide (1-4). Known as a commensal of the digestive and genitourinary tracts of 10 to 30% of the human population, GBS is also a significant source of disease in immunocompromised adults and in the elderly (4-7). Apart from causing human infections, GBS is an etiological agent of bovine mastitis and invasive disease in fish (8-10). F...

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Section: Discussionmentioning

confidence: 63%

Whole-Genome Comparison Uncovers Genomic Mutations between Group B Streptococci Sampled from Infected Newborns and Their Mothers

Almeida¹,

Villain

Joubrel

et al. 2015

J Bacteriol

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“…Our impression is that R3 and Z resemble each other in their physicochemical characterisitcs and, possibly, may belong to a separate GBS protein family. However, the lack of immunological cross-reactivity between them, like the cross-reactivity which exists between different alpha-like proteins (17,18), indicates considerable structural dissimilarity. Sequencing of the encoding genes is required to establish if there is a structural relationship between Z and R3.…”

Section: Discussionmentioning

confidence: 99%

“…The extract (1.5 ml) was applied to the column, which was eluted (8 drops min Ϫ1 , 2-ml fractions) with PBS-NaN 3 , and monitoring was at 280 nm. Ion-exchange chromatography of the materials that eluted from the Sephacryl column was performed as described previously (17). Briefly, DEAE Sephacel (Amersham Pharmacia Biotech AB), 10 mM Tris buffer (pH 8.0) as basic buffer, and elution with stepwise increments of NaCl concentrations up to 1.0 M in the basic buffer were used (17).…”

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confidence: 99%

“…Ion-exchange chromatography of the materials that eluted from the Sephacryl column was performed as described previously (17). Briefly, DEAE Sephacel (Amersham Pharmacia Biotech AB), 10 mM Tris buffer (pH 8.0) as basic buffer, and elution with stepwise increments of NaCl concentrations up to 1.0 M in the basic buffer were used (17). The fractions with eluates were diluted 1:5 in coating buffer, applied to the microtiter plates for coating, and tested against the appropriate antibodies.…”

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confidence: 99%

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Putative Novel Surface-Exposed Streptococcus agalactiae Protein Frequently Expressed by the Group B Streptococcus from Zimbabwe

Mavenyengwa

Mæland

Moyo

2009

Clin Vaccine Immunol

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Group B streptococci (GBS) express a variety of surface-exposed and strain-variable proteins which function as phenotypic markers and as antigens which are able to induce protective immunity in experimental settings. Among these proteins, the chimeric and immunologically cross-reacting alpha-like proteins are particularly important. Another protein, R3, which has been less well studied, occurred at a frequency of 21.5% in GBS from Zimbabwe and, notably, occurred in serotype V strains at a frequency of 75.9%. Working with rabbit antiserum raised against the R3 reference strain ATCC 49447 (strain 10/84; serotype V/R3) to detect the expression of the R3 protein, we recorded findings which suggested that strain 10/84 expressed a strain-variable protein antigen, in addition to R3. The antigen was detected by various enzyme-linked immunosorbent assay-based tests by using acid extract antigens or GBS whole-cell coats and by whole-cell-based Western blotting. We named the putative novel antigen the Z antigen. The Z antigen was a high-molecular-mass antigen that was susceptible to degradation by pepsin and trypsin but that was resistant to m-periodate oxidation and failed to show immunological cross-reactivity with any of a variety of other GBS protein antigens. The Z antigen was expressed by 33/121 (27.2%) of strains of a Zimbabwean GBS strain collection and by 64.2% and 72.4% of the type Ib and type V strains, respectively, and was occasionally expressed by GBS of other capsular serotypes. Thus, the putative novel GBS protein named Z showed distinct capsular antigen associations and presented as an important phenotypic marker in GBS from Zimbabwe. It may be an important antigen in GBS from larger areas of southern Africa. Its prevalence in GBS from Western countries is not known.Streptococcus agalactiae (the group B streptococcus [GBS]) possesses genotypic and phenotypic markers which are important in epidemiological settings. Among the established phenotypic markers, the capsular polysaccharides (CPSs) Ia, Ib, and II through IX play prominent roles in the classification of GBS, in the pathogenesis of GBS disease, and as targets of protective antibodies (15). A variety of surface-anchored and strain-variable proteins are also important GBS markers. These proteins make it possible to define GBS serosubtypes within each CPS type by using antibody-based or gene-based methods for subtyping (6, 11 19, 22). These proteins include Cß and the alpha-like proteins (Alps) C␣, Alp1 (formerly epsilon), Alp2 and Alp3 (formerly probably R1), and Rib (another designation for the R4 protein) (28). The Alps are characterized, among other ways, by a repeat-containing region which has a causal relation to the ladder-like patterns formed by these proteins on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) and Western blotting. The Alps possess chimeric sequences, show variable immunological crossreactivities, and induce increased resistance to GBS infections in experimental models (1,13,15,18,30). For this reason, th...

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“…However, the immunological uniqueness of the proteins Z1, Z2, and R3, indicated by the data of this and earlier studies (9,11), suggests that it may become possible to develop molecular typing methods for specific detection of each of the protein-encoding genes, perhaps by including primer sets for the genes in a multiplex PCR. This prediction is based on data which indicate that at least some strain-variable GBS genes which can be identified by gene-specific PCR often encode proteins which possess protein-specific epitopes (20,21,28,29). Knowledge of the usefulness of Z1, Z2, and R3 determination in GBS serotyping is sparse and unknown for GBS from most areas of the world (9)(10)(11)(12)30).…”

Section: Discussionmentioning

confidence: 99%

Novel Aspects of the Z and R3 Antigens of Streptococcus agalactiae Revealed by Immunological Testing

Mæland

Radtke

Lyng

et al. 2013

Clin Vaccine Immunol

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Group B streptococci (GBS) are important human and bovine pathogens which can be classified by a variety of phenotype-and gene-based techniques. The capsular polysaccharide and strain-variable, surface-anchored proteins are particularly important phenotypic markers. In an earlier study, a previously unrecognized protein antigen called Z was described. It was expressed by 27.2% of GBS strains from Zimbabwe, usually in combination with R3 protein expression. In this study, a putative Z-specific antiserum actually contained antibodies against two different antigens named Z1 and Z2; Z1 was >250 kDa in molecular mass. Z1, Z2, and R3 generated multiple stained bands on Western blots and showed similar chromatographic characteristics with respect to molecular mass, aggregate formation, and charge. Of 28 reference and prototype GBS strains examined, 8/28 (28.5%) isolates expressed one, two, or all three of the Z1, Z2, and R3 antigens; 4/28 expressed all three antigens; 2/28 expressed Z2 and R3; 1/28 expressed Z1 only; and 1/28 expressed R3 only. Twenty (71.5%) of the 28 isolates expressed none of the three antigens. Expression of one or more of these antigens was shown by isolates of the capsular polysaccharide types Ia, Ib, V, and IX and NT strains and occurred in combination with expression of various other strain-variable and surface-localized protein antigens. When used as serosubtype markers, Z1, Z2, and R3 affected existing GBS serotype designations for some of the isolates. For instance, the R3 reference strain Prague 10/84 (ATCC 49447) changed serotype markers from V/R3 to V/R3, Z1, and Z2. Other isolates may change correspondingly, implying consequences for GBS serotyping and research. S ubspecies classification of Streptococcus agalactiae (group B streptococci [GBS]) is important in epidemiological settingsand in efforts to identify highly virulent variants of the bacterium, which is an important pathogen in humans, notably in neonates. A variety of typing techniques have been used for this purpose, such as phenotypic marker-based and/or gene-based techniques. For instance, by use of antibody-based and molecular methods such as multilocus sequence typing (MLST) (1) or restriction digest pattern (RDP) typing (2), GBS clones with particularly high virulence for neonates have been identified (1, 2). The highly virulent variants have been associated with a gene called srr-2 and expression of a surface-linked marker, the ε antigen, which may contribute to the increased virulence (3). Other gene elements and gene products also characterize the highly virulent GBS isolates (4, 5). In addition to a core genome shared by all GBS, GBS genomes contain a large number of strain-variable genes which may encode virulence factors such as strain-variable and surface-linked proteins which may function as adhesins and/or invasins, as targets of protective antibodies (meaning potential vaccine candidates), as enzymes, and as markers for serosubtyping of GBS already serotyped on the basis of the capsular polysaccharide (CPS) antig...

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Antigenic Determinants of Alpha-Like Proteins of Streptococcus agalactiae

Cited by 13 publications

References 25 publications

Whole-Genome Comparison Uncovers Genomic Mutations between Group B Streptococci Sampled from Infected Newborns and Their Mothers

Whole-Genome Comparison Uncovers Genomic Mutations between Group B Streptococci Sampled from Infected Newborns and Their Mothers

Putative Novel Surface-Exposed Streptococcus agalactiae Protein Frequently Expressed by the Group B Streptococcus from Zimbabwe

Novel Aspects of the Z and R3 Antigens of Streptococcus agalactiae Revealed by Immunological Testing

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