Identification of Group B Streptococcal Sip Protein, Which Elicits Cross-Protective Immunity

Brodeur, Bernard R.; Boyer, Martine; Charlebois, Isabelle; Hamel, Josée; Rioux, Clément R.; Martin, Denis

doi:10.1128/iai.68.10.5610-5618.2000

Cited by 138 publications

(121 citation statements)

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“…As these bands were detected with specific antibodies in the mutant strain only it is possible that they represent aggregated forms of the pro-Lpp. There were no differences in the processing of the nonlipoprotein Sip (Brodeur et al, 2000) in the A909DLgt mutant (Fig. 2c), confirming that aberrant processing is restricted to lipoproteins.…”

Section: Effect Of Lgt Inactivation On Lipoprotein Processingsupporting

confidence: 57%

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Impact of lgt mutation on lipoprotein biosynthesis and in vitro phenotypes of Streptococcus agalactiae

2009

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Although Streptococcus agalactiae, the group B Streptococcus, is a leading cause of invasive neonatal disease worldwide the molecular basis of its virulence is still poorly understood. To investigate the role of lipoproteins in the physiology and interaction of this pathogen with host cells, we generated a mutant S. agalactiae strain (A909DLgt) deficient in the Lgt enzyme and thus unable to lipidate lipoprotein precursors (pro-lipoproteins). The loss of pro-lipoprotein lipidation did not affect the viability of S. agalactiae or its growth in several different media, including cationdepleted media. The processing of two well-characterized lipoproteins, but not a non-lipoprotein, was clearly shown to be aberrant in A909DLgt. The mutant strain was shown to be more sensitive to oxidative stress in vitro although the molecular basis of this increased sensitivity was not apparent. The inactivation of Lgt also resulted in changes to the bacterial cell envelope, as demonstrated by reduced retention of both the group B carbohydrate and the polysaccharide capsule and a statistically significant reduction (P50.0079) in A909DLgt adherence to human endothelial cells of fetal origin. These data confirm that failure to process lipoproteins correctly has pleiotropic effects that may be of significance to S. agalactiae colonization and pathogenesis.

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Section: Effect Of Lgt Inactivation On Lipoprotein Processingsupporting

confidence: 57%

“…Fractions were analysed on 10 % SDS-polyacrylamide gels and stained with Coomassie blue or Western blotted as described by Hamilton et al (2000). Blotted membranes were probed with anti-MtuA antibody ; diluted 1/1000), anti-SAG0808 antibody (Tettelin et al, 2002; diluted 1/1000) or antiSip antibody (Brodeur et al, 2000; diluted 1/500).…”

mentioning

confidence: 99%

Impact of lgt mutation on lipoprotein biosynthesis and in vitro phenotypes of Streptococcus agalactiae

2009

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“…However, strains of GBS also express surface proteins that elicit protective immunity and these proteins have attracted increasing interest for studies of pathogenic mechanisms and for vaccine development (3)(4)(5)(6)(7)(8)(9). One of these proteins is the ␤ protein (also known as Bac or ␤ C), which is of interest not only because it elicits protective immunity but also because it binds to the Fc part of human IgA (10 -14).…”

mentioning

confidence: 99%

Streptococcal β Protein Has Separate Binding Sites for Human Factor H and IgA-Fc

Areschoug

Stålhammar‐Carlemalm

Karlsson

et al. 2002

Journal of Biological Chemistry

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The group B streptococcus (GBS) is the most important cause of life-threatening bacterial infections in newborn infants. Protective immunity to GBS infection is elicited by several surface proteins, one of which, the ␤ protein, is known to bind human IgA-Fc. Here, we show that the ␤ protein also binds human factor H (FH), a negative regulator of complement activation. Absorption experiments with whole human plasma demonstrated binding of FH to a GBS strain expressing ␤ protein but not to an isogenic ␤-negative mutant. This binding was due to a direct interaction between ␤ and FH, as shown by experiments with purified proteins. Inhibition tests and studies with ␤ fragments demonstrated that FH and IgA-Fc bind to separate and nonoverlapping regions in ␤. Heparin, a known ligand for FH, specifically inhibited the binding between ␤ and FH, suggesting that FH has overlapping binding sites for ␤ and heparin. Bacteria-bound FH retained its complement regulatory activity, implying that ␤-expressing GBS may use bound FH to evade complement attack. The finding that ␤ protein binds FH adds to a growing list of interactions between human pathogens and complement regulatory proteins, supporting the notion that these interactions are of general importance in bacterial pathogenesis.

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“…Four antigens were capable of significantly increasing the survival rate among challenged infant mice. Only one of these antigens, the Sip protein that had been previously identified as a potential vaccine antigen [16], was part of the core genome. Each of the genes encoding the other three antigens was present in approximately 75% of strains.…”

Section: Chlamydia Pneumoniaementioning

confidence: 99%

Post‐genomic vaccine development

2006

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For over a century, vaccines were developed according to Pasteur's principles of isolating, inactivating and injecting the causative agent of an infectious disease. The availability of a complete microbial genome sequence in 1995 marked the beginning of a genomic era that has allowed scientists to change the paradigm and approach vaccine development starting from genomic information, a process named reverse vaccinology. This can be considered as one of the most powerful examples of how genomic information can be used to develop therapeutic interventions, which were difficult or impossible to tackle with conventional approaches. As the genomic era progressed, it became apparent that multi-strain genome analysis is fundamental to the design of universal vaccines. In the post-genomic era, the next challenge of the vaccine biologist will be the merging of the vaccinology with structural biology.

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Identification of Group B Streptococcal Sip Protein, Which Elicits Cross-Protective Immunity

Cited by 138 publications

References 40 publications

Impact of lgt mutation on lipoprotein biosynthesis and in vitro phenotypes of Streptococcus agalactiae

Impact of lgt mutation on lipoprotein biosynthesis and in vitro phenotypes of Streptococcus agalactiae

Streptococcal β Protein Has Separate Binding Sites for Human Factor H and IgA-Fc

Post‐genomic vaccine development

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