Embryonic Neural Cell Adhesion Molecule in Cerebrospinal Fluid of Younger Children: Age‐Dependent Decrease During the First Year

Weisgerber, C; Husmann, Matthias; Frosch, Matthias; Rheinheimer, Claudia; Peuckert, W.; Görgen, Ingrid; Bitter‐Suermann, D.

doi:10.1111/j.1471-4159.1990.tb05796.x

Cited by 17 publications

(7 citation statements)

References 56 publications

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“…Endosialidase activity was determined as described earlier (Stummeyer et al ., 2005). Briefly, microtiter plates (Becton Dickinson) were coated for 1 h with 20 µl well −1 purified capsular polysaccharide (1 µg ml −1 ) of E. coli K1 (Weisgerber et al ., 1990). Non‐specific binding sites were blocked with 1% BSA in PBS (10 mM sodium phosphate pH 7.4, 150 mM NaCl) and endosialidase containing samples were applied for 30 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Evolution of bacteriophages infecting encapsulated bacteria: lessons from Escherichia coli K1‐specific phages

Stummeyer

Schwarzer

Claus

et al. 2006

Molecular Microbiology

105

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SummaryBacterial capsules are not only important virulence factors, but also provide attachment sites for bacteriophages that possess capsule degrading enzymes as tailspike proteins. To gain insight into the evolution of these specialized viruses, we studied a panel of tailed phages specific for Escherichia coli K1, a neuroinvasive pathogen with a polysialic acid capsule. Genome sequencing of two lytic K1-phages and comparative analyses including a K1-prophage revealed that K1-phages did not evolve from a common ancestor. By contrast, each phage is related to a different progenitor type, namely T7-, SP6-, and P22-like phages, and gained new host specificity by horizontal uptake of an endosialidase gene. The new tailspikes emerged by combining endosialidase domains with the capsid binding module of the respective ancestor. For SP6-like phages, we identified a degenerated tailspike protein which now acts as versatile adaptor protein interconnecting tail and newly acquired tailspikes and demonstrate that this adapter utilizes an N-terminal undecapeptide interface to bind otherwise unrelated tailspikes. Combining biochemical and sequence analyses with available structural data, we provide new molecular insight into basic mechanisms that allow changes in host specificity while a conserved head and tail architecture is maintained. Thereby, the present study contributes not only to an improved understanding of phage evolution and hostrange extension but may also facilitate the on purpose design of therapeutic phages based on wellcharacterized template phages.

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Section: Methodsmentioning

confidence: 99%

Evolution of bacteriophages infecting encapsulated bacteria: lessons from Escherichia coli K1‐specific phages

Stummeyer

Schwarzer

Claus

et al. 2006

Molecular Microbiology

105

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“…(1987). Endo NE was purified by a modification of previous protocols (Tomlinson and Taylor, 1985;Weisgerber et at., 1990). To produce phage lysates.…”

Section: Purification Of Sendo Ne and Sendo Nfmentioning

confidence: 99%

Molecular cloning and functional expression of bacteriophage PK1E‐encoded endoneuraminidase Endo NE

Gerardy‐Schahn

Bethe

Brennecke

et al. 1995

Molecular Microbiology

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Homopolymeric alpha-2,8-linked sialic acid (PSA) has been found as a capsular component of sepsis- and meningitis-causing bacterial pathogens, and on eukaryotic cells as a post-translational modification of the neural cell adhesion molecule (NCAM). The polysaccharide is specifically recognized and degraded by a phage-encoded enzyme, the endo-N-acetylneuraminidase E (Endo NE). Endo NE therefore has become a valuable tool in the study of bacterial pathogenesis and eukaryotic morphogenesis. In this report we describe the molecular cloning of Endo NE and the expression of a functionally active recombinant enzyme. The cloned DNA sequence (2436 bp) encodes a polypeptide of 811 amino acids, which at the 5' end contains a totally conserved neuraminidase motif. Expressed in Escherichia coli, the enzyme migrates as a single band of approximately 74 kDa in SDS-PAGE. A central domain of 669 amino acid residues is about 90% homologous to the recently cloned Endo NF. Both phage-induced lysis of bacteria and the catalysis of PSA degradation by the recombinant enzyme are efficiently inhibited by a polyclonal antiserum raised against the intact phage particle. The C-terminal region seems to be essential to enzymatic functions, as truncation of 32 amino acids outside the homology domain completely abolishes Endo NE activity. Our data also indicate that the 38 kDa protein, previously assumed to be a subunit of the Endo NE holoenzyme, is the product of a separate gene locus and is not necessary for in vitro depolymerase activity.

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“…Serogroup B capsular polysaccharide is not effective as a vaccine in part because it is structurally similar to host neural-cell adhesion molecule and is therefore poorly immunogenic (5). Reverse vaccinology has identified a lipoprotein called GNA1870, also known as lipoprotein 2086 (6), that is surface expressed on all meningococcal strains tested and elicits bactericidal Abs that are protective in the infant rat model of meningococcal bacteremia (6 -9).…”

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confidence: 99%

The Meningococcal Vaccine Candidate GNA1870 Binds the Complement Regulatory Protein Factor H and Enhances Serum Resistance

Madico

Welsch²,

Lewis

et al. 2006

The Journal of Immunology

367

432

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Neisseria meningitidis binds factor H (fH), a key regulator of the alternative complement pathway. A ∼29 kD fH-binding protein expressed in the meningococcal outer membrane was identified by mass spectrometry as GNA1870, a lipoprotein currently under evaluation as a broad-spectrum meningococcal vaccine candidate. GNA1870 was confirmed as the fH ligand on intact bacteria by 1) abrogation of fH binding upon deleting GNA1870, and 2) blocking fH binding by anti-GNA1870 mAbs. fH bound to whole bacteria and purified rGNA1870 representing each of the three variant GNA1870 families. We showed that the amount of fH binding correlated with the level of bacterial GNA1870 expression. High levels of variant 1 GNA1870 expression (either by allelic replacement of gna1870 or by plasmid-driven high-level expression) in strains that otherwise were low-level GNA1870 expressers (and bound low amounts of fH by flow cytometry) restored high levels of fH binding. Diminished fH binding to the GNA1870 deletion mutants was accompanied by enhanced C3 binding and increased killing of the mutants. Conversely, high levels of GNA1870 expression and fH binding enhanced serum resistance. Our findings support the hypothesis that inhibiting the binding of a complement down-regulator protein to the neisserial surface by specific Ab may enhance intrinsic bactericidal activity of the Ab, resulting in two distinct mechanisms of Ab-mediated vaccine efficacy. These data provide further support for inclusion of this molecule in a meningococcal vaccine. To reflect the critical function of this molecule, we suggest calling it fH-binding protein.

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Embryonic Neural Cell Adhesion Molecule in Cerebrospinal Fluid of Younger Children: Age‐Dependent Decrease During the First Year

Cited by 17 publications

References 56 publications

Evolution of bacteriophages infecting encapsulated bacteria: lessons from Escherichia coli K1‐specific phages

Evolution of bacteriophages infecting encapsulated bacteria: lessons from Escherichia coli K1‐specific phages

Molecular cloning and functional expression of bacteriophage PK1E‐encoded endoneuraminidase Endo NE

The Meningococcal Vaccine Candidate GNA1870 Binds the Complement Regulatory Protein Factor H and Enhances Serum Resistance

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