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Survey of immunological features of the alpha-like proteins of Streptococcus agalactiae.

ABSTRACT: Nearly all Streptococcus agalactiae (group B streptococcus [GBS]) strains express a protein which belongs to the so-called alpha-like proteins (Alps), of which C?, Alp1, Alp2, Alp3, Rib, and Alp4 are known to occur in GBS. The Alps are chimeras which form mosaic structures on the GBS surface. Both N- and C-terminal stretches of the Alps possess immunogenic sites of dissimilar immunological specificity. In this review, we have compiled data dealing with the specificity of the N- and C-terminal immunogenic sites of the Alps. The majority of N-terminal sites show protein specificity while the C-terminal sites show broader cross-reactivity. Molecular serotyping has revealed that antibody-based serotyping has often resulted in erroneous Alp identification, due to persistence of cross-reacting antibodies in antisera for serotyping. Retrospectively, this could be expected on the basis of sequence analysis results. Some of the historical R proteins are in fact Alps. The data included in the review may provide a basis for decisions regarding techniques for the preparation of specific antisera for serotyping of GBS, for use in other approaches in GBS research, and for decision making in the context of GBS vaccine developments.

SUBMITTER: Maeland JA

PROVIDER: S-EPMC4308872 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Survey of immunological features of the alpha-like proteins of Streptococcus agalactiae.

Maeland Johan A JA Afset Jan E JE Lyng Randi V RV Radtke Andreas A

Clinical and vaccine immunology : CVI 20141224 2

Nearly all Streptococcus agalactiae (group B streptococcus [GBS]) strains express a protein which belongs to the so-called alpha-like proteins (Alps), of which Cα, Alp1, Alp2, Alp3, Rib, and Alp4 are known to occur in GBS. The Alps are chimeras which form mosaic structures on the GBS surface. Both N- and C-terminal stretches of the Alps possess immunogenic sites of dissimilar immunological specificity. In this review, we have compiled data dealing with the specificity of the N- and C-terminal im ...[more]

PMID: 25540270

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Project description:This study focuses on immunological markers of R4, an important Streptococcus group B (GBS) protein. The results obtained by using rabbit antisera and purified proteins for antigens in enzyme-linked immunosorbent assay-based experiments provided evidence that R4 possesses two antigenic determinants. One of the determinants is shared with the alpha-like protein 3 (Alp3) of GBS, was named R4/Alp3 common, and was expressed by GBS, which possessed the Alp3-encoding gene alp3 or the R4-encoding gene rib. The other antigenic determinant was detected only in rib-positive GBS organisms and was named R4 specific. This determinant probably is an immunological marker unique to the R4 protein. Neither of the antigenic R4 determinants showed serological cross-reactivity with the GBS proteins Calpha, Cbeta, and R3 or with alpha-like protein 2. Of 60 clinical serotype III GBS strains, 56 (93%) isolates possessed the rib gene and 50 (89%) of the rib-positive isolates expressed levels of R4 detectable by antibody-based tests, consistent with R4 expression failure or low-level expression in approximately 10% of rib-positive GBS. alp3 was not detected in type III GBS but was possessed by six of eight type V strains and six of six type VIII strains. All alp3-positive strains were recognized by the R4/Alp3 common antibodies, but none of them were recognized by the R4-specific antibodies. NCTC 9828, a reference strain for R3 and R4, expressed the determinant R4/Alp3 common but not R4 specific. A monoclonal R4 antibody, previously considered to be R4 specific and used in GBS serotyping, targeted R4/Alp3 common and is thus not R4 specific. The results show that failure to discriminate between R4 specific and R4/Alp3 common by antisera designed for GBS serotyping can result in the false identification of Alp3 as R4 or vice versa, whereas anti-R4 antibodies targeting only the determinant R4 specific will detect only R4. Both R4 and Alp3 need further evaluation with respect to the immunobiological function of each distinct antigenic determinant, for instance, with regard to their potential as GBS vaccine components.

Project description:BackgroundStreptococcus agalactiae (Group B Streptococcus, GBS) serotypes, sequence types, and antimicrobial resistance profile vary across different geographic locations affecting disease patterns in newborns. These differences are important considerations for vaccine development efforts and data from large countries in Africa is limited. The aim of this study was to determine serotypes and genotypes of GBS isolates from pregnant women and their newborns in Ethiopia.MethodsA hospital based cross-sectional study was conducted at three hospitals in Ethiopia from June 2014 to September 2015. Out of 225 GBS isolates, 121 GBS were recovered, confirmed and characterized at CDC's Streptococcus Laboratory using conventional microbiology methods and whole genome sequencing.ResultsOf the 121 isolates, 87 were from rectovaginal samples of pregnant women, 32 from different body parts of their newborns and 2 from blood of newborns with suspected sepsis. There were 25 mother-infant pairs and 24 pairs had concordant strains. The most prevalent serotypes among mothers and/or their babies were II, Ia and V (41.5, 20.6, 19.5 and 40.6%, 25 and 15.6%, respectively). Multilocus sequence typing (MLST) on 83 isolates showed ST10 (24; 28.9%) and ST2 (12; 14.5%) as most predominant sequence types. All GBS strains were susceptible to penicillin, cefotaxime and vancomycin, which correlated to the presence of wildtype PBP2x types and the lack of known vancomycin-resistance genes. Tetracycline resistance was high (73; 88%, associated primarily with tetM, but also tetO and tetL). Five isolates (6%) were resistant to erythromycin and clindamycin and 3 isolates were fluoroquinolone-resistant, containing associated mutations in gyrA and parC genes. All isolates were positive for one of four homologous Alpha/Rib family determinants and 1-2 of the three main pilus types.ConclusionsPredominant serotypes were II, Ia, and V. A limited number of clonal types were identified with two STs accounting for about half of the isolates. All strains collected in this study were susceptible to beta-lactam antibiotics and vancomycin. Typical of most GBS, these isolates were positive for single alpha-like family protein, serine-rich repeat gene, as well as 1-2 pilus determinants.

Dataset Information

Survey of immunological features of the alpha-like proteins of Streptococcus agalactiae.

Publications

Survey of immunological features of the alpha-like proteins of Streptococcus agalactiae.

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