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Mosaicism in the alpha-like protein genes of group B streptococci.

ABSTRACT: Members of a family of repeat-containing surface proteins of group B streptococci (GBS) defined by the alpha C and Rib proteins exhibit size variability and cross-reactivity and have been studied as potential vaccine components. We report evidence of horizontal DNA transfer with subsequent recombination as a mechanism generating diversity within this antigen family. Alp2 and Alp3 are additional members of the alpha C protein family identified in strains of the emerging GBS serotypes V and VIII. Each contains an overall genetic organization highly similar to that of the alpha C and Rib proteins, including a tandem repeat region and conserved N- and C-terminal regions. Among different strains, protein size varies according to the number of tandem repeats within the corresponding gene. Unlike the alpha C and Rib proteins, however, the newly described alpha-like proteins contain other regions, including one similar to the IgA-binding region of the GBS beta C protein, a nontandem repeat region, and an isolated repeat highly homologous to the alpha C repeat. Sequence analysis of the regions flanking the alpha C protein gene on a 13.7-kb insert reveals several ORFs that are likely to be involved in basic metabolic pathways. Analysis of corresponding flanking regions in other GBS strains, including the parent strains of the newly described alpha-like proteins, shows striking conservation among all strains studied. These findings indicate that the alpha-like proteins are encoded by mosaic variants at a single genomic locus and suggest that recombination after horizontal DNA transfer is a means of generating diversity within this protein family.

SUBMITTER: Lachenauer CS

PROVIDER: S-EPMC16916 | biostudies-literature | 2000 Aug

REPOSITORIES: biostudies-literature

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Mosaicism in the alpha-like protein genes of group B streptococci.

Lachenauer C S CS Creti R R Michel J L JL Madoff L C LC

Proceedings of the National Academy of Sciences of the United States of America 20000801 17

Members of a family of repeat-containing surface proteins of group B streptococci (GBS) defined by the alpha C and Rib proteins exhibit size variability and cross-reactivity and have been studied as potential vaccine components. We report evidence of horizontal DNA transfer with subsequent recombination as a mechanism generating diversity within this antigen family. Alp2 and Alp3 are additional members of the alpha C protein family identified in strains of the emerging GBS serotypes V and VIII. ...[more]

PMID: 10944228

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Project description:Streptococcus dysgalactiae subsp. equeisimilis (SDSE) has Lancefield group G or C antigens. Recent epidemiological studies reveal that invasive SDSE infections have been increasing in Asia, Europe and US. Although SDSE possesses similar virulence factors to S. pyogenes including streptolysin S (SLS) and streptolysin O (SLO), some important S. pyogenes virulence factors including active superantigens, SpeB and a hyarulonic acids capsule are missing in SDSE genome. The mechanisms and the key virulence factors for causing invasive diseases by SDSE are poorly understood. Here, we analyzed the transcriptome of SDSE in vivo using the murine sepsis model, revealing the strategy of SDSE to destruct host tissues with the virulence factors and to scavenge depleted nutrients. The expression of SLO operon increased at relatively early stage of infection while the SLS and hyaluronidases upregulated after 4h post infection. Microarray data suggested that SDSE degraded host tissue polysaccharides by streptococcal-secreting poly/oligosaccharide lyases and simultaneously used the Entner-Doudoroff pathway to metabolize acquired carbohydrates. A global negative virulence gene regulator CsrRS of SDSE modulated the expressions of genes encoding SLS and the carbohydrate metabolism enzymes. Moreover, csrS deficient mutant induced sever systemic hemolysis in mice. The most frequently isolated stG6792 strains from invasive disease secreted abundant SLS and SLO rather than other SDSE emm types, indicating the relationship between the SLS and SLO productions and poor outcome by the stG6792 strain infection. Our findings suggest that the concomitant regulation of virulence factors destructing the host tissues and metabolic enzymes play an important role to produce invasive diseases by SDSE. To analyze gene expressions in group G streptococci with the murine infection model, we developed a custom microarray for Streptococcus dysgalactiae subsp. equisimilis (SDSE) based on the genome sequences of three SDSE strains; GGS_124, ATCC12923 and RE378. We intraperitoneally inoculated 10^8 CFU of GGS_124 stain and the csrS deficient mutant into ddY mice. Bacterial cells were collected from the abdominal cavity at 0, 2, 4 and 8 h post infection. GGS_124 cells were also collected from OD600=0.6 culture in brain heart infusion broth as a control.

Dataset Information

Mosaicism in the alpha-like protein genes of group B streptococci.

Publications

Mosaicism in the alpha-like protein genes of group B streptococci.

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