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Streptococcus dysgalactiae subsp. equisimilis (SDSE) is a human pathogen that colonizes the skin or throat, and causes a range of diseases from relatively benign pharyngitis to potentially fatal invasive diseases. While not as virulent as the close relative Streptococcus pyogenes the two share a number of virulence factors and are known to coexist in a human host. Both pre- and post-genomic studies have revealed that horizontal gene transfer (HGT) and recombination occurs between these two organisms and plays a major role in shaping the population structure of SDSE. This review summarizes our current knowledge of HGT and recombination in the evolution of SDSE. [ABSTRACT FROM AUTHOR]

Streptococcus pyogenes ranks among the main causes of mortality from bacterial infections worldwide. Currently there is no vaccine to prevent diseases such as rheumatic heart disease and invasive streptococcal infection. The streptococcal M protein that is used as the substrate for epidemiological typing is both a virulence factor and a vaccine antigen. Over 220 variants of this protein have been described, making comparisons between proteins difficult, and hindering M protein-based vaccine development. A functional classification based on 48 emm-clusters containing closely related M proteins that share binding and structural properties is proposed. The need for a paradigm shift from type-specific immunity against S. pyogenes to emm-cluster based immunity for this bacterium should be further investigated. Implementation of this emm-cluster-based system as a standard typing scheme for S. pyogenes will facilitate the design of future studies of M protein function, streptococcal virulence, epidemiological surveillance, and vaccine development. [ABSTRACT FROM AUTHOR]

Background. In spite of the emerging importance of Streptococcus dysgalactiae subspecies equisimilis (human group C streptococci [GCS] and group G streptococci [GGS]) in human health, its molecular makeup remains largely undefined. Apart from sharing a phylogenetic relationship with the human pathogen group A streptococci (GAS), GCS/GGS and GAS colonize the same ecological niche and exhibit considerable overlap in their disease profiles. Such similarities imply that the virulence factors associated with diseases may also be similar. Methods. In this study, we used a targeted microarray containing 216 GAS virulence genes to profile the virulence gene repertoires of 58 S. dysgalactiae subspecies equisimilis isolates recovered during human infections. We performed comparative analyses to investigate the relationship between GAS virulence genes in and the invasive potential of GCS/GGS. Results. Up to one-half of the GAS virulence genes represented in the microarray were identified in GCS/GGS. No statistical differences were observed between isolates harboring the group C versus group G carbohydrates; however, clustering algorithms revealed 2 genetically distinct clusters of S. dysgalactiae subspecies equisimilis isolates. No relationship was observed between the virulence profile of GCS/GGS and the propensity for disease or the tissue site of isolation. Conclusions. This is, to our knowledge, the first comprehensive analysis of the virulence profile of S. dysgalactiae subspecies equisimilis, and it enables novel insights into the pathogen's genetic basis of disease propensity shared with GAS. Human group C and group G streptococci may not be considered to be separate species; in fact, they may constitute 2 distinct lineages. Additional incongruent relationships were observed between virulence profiles and GCS/GGS disease propensity. [ABSTRACT FROM AUTHOR]

Abstract: Streptococcus dysgalactiae, subsp. equisimilis elicit a range of clinical manifestations similar to that of their close genetic relatives, group A streptococcus (GAS). The similarity in disease profiles raises questions as to the degree of genetic similarity between these two human pathogens, particularly in relation to virulence gene repertoires. In this study, we use a group A streptococcal virulence array comprising of 60 genes previously described as GAS virulence factors, and another 159 genes predicted to encode for extracellular proteins to examine the extent of their occurrence in 58 S. dysgalactiae subsp. equisimilis isolates. Between 25% and 50% of the genes represented on the array were present in the S. dysgalactiae subsp. equisimilis isolates. These observations highlight the similar virulence attributes of closely related human pathogenic streptococci. [Copyright &y& Elsevier]

Abstract: We have constructed a targeted GAS virulence array containing 228 group A streptococcal genes. Using this array we profiled the virulence gene repertoire of 45 GAS isolates from The Netherlands. Cluster analysis of the array data for these strains successfully grouped strains by emm-type. Statistical analysis of the distribution of genes between emm-types showed that bacteriophage related genes were a significant contributor to the inter-emm-type genetic variation. However we also identified a number of non-phage genes whose distribution varied between emm-types. We hypothesise that these genes may be remnant or uncharacterised phage-related genes. [Copyright &y& Elsevier]

Abstract: A conformationally restricted B cell epitope has been identified as a potential safe vaccine candidate from the major group A streptococcal virulence factor, the M protein. To maintain α-helical secondary structure, the minimal epitope is flanked with heterologous sequences to produce the chimeric vaccine candidate called J14. As a strategy toward developing an affordable multivalent GAS vaccine, we have expressed J14 recombinantly with a second GAS protective antigen H12 (rJ14H12). When administered to mice sub-cutaneously, the fusion protein stimulated a strong serum IgG response to the H12 component, but J14 was poorly immunogenic. To increase the immunogenicity of J14 when expressed with the model fusion partner, amino acid modifications were made to the initial recombinant J14 construct to produce rJJo. These changes stabilised the α-helical conformation of the recombinant antigen as assessed by circular dichroism. Mice immunised with rJJoH12, the fusion protein incorporating JJo, effectively stimulated a humoral response to both of the included antigens. These data support the feasibility of developing a multivalent vaccine incorporating the conformationally restricted protective antigen J14. [Copyright &y& Elsevier]

Lateral gene transfer is a significant contributor to the ongoing evolution of many bacterial pathogens, including β-hemolytic streptococci. Here we provide the first characterization of a novel integrative conjugative element (ICE), ICESde3396, from Streptococcus dysgalactiae subsp. equisimilis (group G streptococcus [GGS]), a bacterium commonly found in the throat and skin of humans. ICESde3396 is 64 kb in size and encodes 66 putative open reading frames. ICESde3396 shares 38 open reading frames with a putative ICE from Streptococcus agalactiae (group B streptococcus [GBS]), ICESa2603. In addition to genes involves in conjugal processes, ICESde3396 also carries genes predicted to be involved in virulence and resistance to various metals. A major feature of ICESde3396 differentiating it from ICESa2603 is the presence of an 18-kb internal recombinogenic region containing four unique gene clusters, which appear to have been acquired from streptococcal and nonstreptococcal bacterial species. The four clusters include two cadmium resistance operons, an arsenic resistance operon, and genes with orthologues in a group A streptococcus (GAS) prophage. Streptococci that naturally harbor ICESde3396 have increased resistance to cadmium and arsenate, indicating the functionality of genes present in the 18-kb recombinogenic region. By marking ICESde3396 with a kanamycin resistance gene, we demonstrate that the ICE is transferable to other GGS isolates as well as GBS and GAS. To investigate the presence of the ICE in clinical streptococcal isolates, we screened 69 isolates (30 GGS, 19 GBS, and 20 GAS isolates) for the presence of three separate regions of ICESde3396. Eleven isolates possessed all three regions, suggesting they harbored ICESde3396-like elements. Another four isolates possessed ICESa2603-like elements. We propose that ICESde3396 is a mobile genetic element that is capable of acquiring DNA from multiple bacterial sources and is a vehicle for dissemination of this DNA through the wider β-hemolytic streptococcal population. [ABSTRACT FROM AUTHOR]