scholarly journals Genetic diversity of the C protein β-antigen gene and its upstream regions within clonally related groups of type Ia and Ib group B streptococci

Microbiology ◽  
2006 ◽  
Vol 152 (3) ◽  
pp. 771-778 ◽  
Author(s):  
Noriyuki Nagano ◽  
Yukiko Nagano ◽  
Ryuichi Nakano ◽  
Ryoichi Okamoto ◽  
Matsuhisa Inoue

C protein β antigen (Bac), a surface protein of group B streptococci (GBS), is known to concurrently bind the Fc portion of IgA and factor H (FH). The authors' previous work has demonstrated that mRNA expression levels show diversity among clonally related strains containing genes (bac) encoding Bac, with high expression noted in invasive strains. In this study, the bac gene and upstream regions containing putative promoters, three ORFs and an IS1381 insertion sequence were characterized. Three invasive strains showed high bac expression levels and did not show any notable mutations except one strain producing Bac that was able to bind FH but not IgA. A deletion of 51 amino acid residues, including part of the Bac IgA-binding region, was identified and hypothesized to contribute to the loss of the IgA-binding ability of this strain. A vaginal strain that showed somewhat higher bac expression levels and produced Bac lacking immunoreactivity contained an 11 bp deletion, which generated a premature termination codon, in the region preceding the IgA-binding region. In another vaginal strain that did not express bac, disruption of the upstream ORFs of the sensor histidine kinase and DNA-binding response regulator, due to frameshift mutations, was noted although it is not known whether these proteins directly affect bac expression levels. An IS1381 insertion into the promoter region was found in another vaginal strain that showed low expression levels and produced Bac with a significantly larger proline-rich repeat region. These results demonstrate considerable genetic diversity of the bac and upstream regions of invasive and noninvasive GBS, which may contribute to the variability of bac expression levels among those strains.

1999 ◽  
Vol 67 (5) ◽  
pp. 2491-2496 ◽  
Author(s):  
Claudia Gravekamp ◽  
Dennis L. Kasper ◽  
Lawrence C. Paoletti ◽  
Lawrence C. Madoff

ABSTRACT The alpha C protein, a protective surface protein of group B streptococci (GBS), is present in most non-type III GBS strains. Conjugate vaccines composed of the alpha C protein and type III capsular polysaccharide (CPS) might be protective against most GBS infections. In this study, the type III CPS was covalently coupled to full-length, nine-repeat alpha C protein (resulting in III-α9r conjugate vaccine) or to two-repeat alpha C protein (resulting in III-α2r conjugate vaccine) by reductive amination. Initial experiments with the III-α9r vaccine showed that it was poorly immunogenic in mice with respect to both vaccine antigens and was suboptimally efficacious in providing protection in mice against challenge with GBS. Therefore, modified vaccination protocols were used with the III-α2r vaccine. Female mice were immunized three times with 0.5, 5, or 20 μg of the III-α2r vaccine with an aluminum hydroxide adjuvant and bred. Ninety-five percent of neonatal mice born to dams immunized with the III-α2r vaccine survived challenge with GBS expressing type III CPS, and 60% survived challenge with GBS expressing wild-type (nine-repeat) alpha C protein; 18 and 17%, respectively, of mice in the negative control groups survived (P, <0.0001). These protection levels did not differ significantly from those obtained with the type III CPS-tetanus toxoid conjugate vaccine and the unconjugated two-repeat alpha C protein, which protected 98 and 58% of neonates from infection with GBS expressing type III CPS or the alpha C protein, respectively. Thus, the two-repeat alpha C protein in the vaccine was immunogenic and simultaneously enhanced the immunogenicity of type III CPS. III-α vaccines may be alternatives to GBS polysaccharide-tetanus toxoid vaccines, eliciting additional antibodies protective against GBS infection.


1991 ◽  
Vol 59 (6) ◽  
pp. 2023-2028 ◽  
Author(s):  
J L Michel ◽  
L C Madoff ◽  
D E Kling ◽  
D L Kasper ◽  
F M Ausubel

2009 ◽  
Vol 23 (11) ◽  
pp. 3967-3977 ◽  
Author(s):  
Ravi Maruvada ◽  
Nemani V. Prasadarao ◽  
C. E. Rubens

1998 ◽  
Vol 66 (9) ◽  
pp. 4347-4354
Author(s):  
C. Gravekamp ◽  
Bernard Rosner ◽  
L. C. Madoff

1993 ◽  
Vol 46 (7) ◽  
pp. 633-636 ◽  
Author(s):  
J A Mawn ◽  
A J Simpson ◽  
S R Heard

2015 ◽  
Vol 197 (20) ◽  
pp. 3354-3366 ◽  
Author(s):  
Alexandre Almeida ◽  
Adrien Villain ◽  
Caroline Joubrel ◽  
Gérald Touak ◽  
Elisabeth Sauvage ◽  
...  

ABSTRACTStreptococcus agalactiae(group BStreptococcusor 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 thecovRSlocus, 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 BStreptococcus(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.


1996 ◽  
Vol 93 (9) ◽  
pp. 4131-4136 ◽  
Author(s):  
L. C. Madoff ◽  
J. L. Michel ◽  
E. W. Gong ◽  
D. E. Kling ◽  
D. L. Kasper

2014 ◽  
Vol 69 (6) ◽  
pp. 894-898
Author(s):  
Aurea E. Flores ◽  
G. S. Chhatwal ◽  
Sharon L. Hillier ◽  
Carol J. Baker ◽  
Patricia Ferrieri

Sign in / Sign up

Export Citation Format

Share Document