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Invasive potential of nonencapsulated disease isolates of Neisseria meningitidis.

https://arctichealth.org/en/permalink/ahliterature125182
Source
Infect Immun. 2012 Jul;80(7):2346-53
Publication Type
Article
Date
Jul-2012
Author
Kay O Johswich
Jianwei Zhou
Dennis K S Law
Frank St Michael
Shannon E McCaw
Frances B Jamieson
Andrew D Cox
Raymond S W Tsang
Scott D Gray-Owen
Author Affiliation
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Source
Infect Immun. 2012 Jul;80(7):2346-53
Date
Jul-2012
Language
English
Publication Type
Article
Keywords
Animals
Bacterial Capsules - genetics - immunology - metabolism
Canada
Complement System Proteins - immunology
Disease Models, Animal
Female
Genes, Bacterial
Humans
Male
Meningococcal Infections - microbiology - mortality
Mice
Mice, Inbred C57BL
Neisseria meningitidis - immunology - isolation & purification - pathogenicity
Peritonitis - microbiology - mortality
Polymerase Chain Reaction
Rabbits
Serotyping
Survival Analysis
Virulence Factors - deficiency - immunology - metabolism
Abstract
The capsule of Neisseria meningitidis is the major virulence factor that enables this bacterium to overcome host immunity elicited by complement and phagocytes, rendering it capable of surviving in blood. As such, nonencapsulated N. meningitidis isolates are generally considered nonpathogenic. Here, we consider the inherent virulence of two nonencapsulated N. meningitidis isolates obtained from our national surveillance of infected blood cultures in Canada. Capsule deficiency of both strains was confirmed by serology and PCR for the ctrA to ctrD genes and siaA to siaC genes, as well as siaD genes specific to serogroups B, C, Y, and W135. In both strains, the capsule synthesis genes were replaced by the capsule null locus, cnl-2. In accordance with a lack of capsule, both strains were fully susceptible to killing by both human and baby rabbit complement. However, in the presence of cytidine-5' monophospho-N-acetylneuraminic acid (CMP-NANA), allowing for lipooligosaccharide (LOS) sialylation, a significant increase of resistance to complement killing was observed. Mass spectrometry of purified LOS did not reveal any uncommon modifications that would explain their invasive phenotype. Finally, in a mouse intraperitoneal challenge model, these nonencapsulated isolates displayed enhanced virulence relative to an isogenic mutant of serogroup B strain MC58 lacking capsule (MC58?siaD). Virulence of all nonencapsulated isolates tested was below that of encapsulated serogroup B strains MC58 and B16B6. However, whereas no mortality was observed with MC58?siaD, 5/10 mice succumbed to infection with strain 2275 and 2/11 mice succumbed to strain 2274. Our results suggest the acquisition of a new virulence phenotype by these nonencapsulated strains.
Notes
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PubMed ID
22508859 View in PubMed
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Investigating the candidacy of a capsular polysaccharide-based glycoconjugate as a vaccine to combat Haemophilus influenzae type a disease: A solution for an unmet public health need.

https://arctichealth.org/en/permalink/ahliterature290367
Source
Vaccine. 2017 10 27; 35(45):6129-6136
Publication Type
Journal Article
Date
10-27-2017
Author
Andrew D Cox
Dean Williams
Chantelle Cairns
Frank St Michael
Perry Fleming
Evgeny Vinogradov
Mélanie Arbour
Luke Masson
Wei Zou
Author Affiliation
Vaccine Program, Human Health Therapeutics Portfolio, National Research Council, Ottawa, ON K1A 0R6, Canada. Electronic address: Andrew.Cox@nrc-cnrc.gc.ca.
Source
Vaccine. 2017 10 27; 35(45):6129-6136
Date
10-27-2017
Language
English
Publication Type
Journal Article
Keywords
Alaska
Animals
Bacterial Capsules - immunology
Canada
Female
Glycoconjugates - immunology
Haemophilus Infections - immunology - prevention & control
Haemophilus Vaccines - immunology
Haemophilus influenzae - immunology
Humans
Mice
Mice, Inbred BALB C
Polysaccharides, Bacterial - immunology
Public Health
Rabbits
Serotyping - methods
Vaccination - methods
Abstract
After the introduction of the glycoconjugate vaccine based upon the capsular polysaccharide ofHaemophilus influenzaetype b in the mid 1980s there was a remarkable decrease in the number of invasive cases reported for this organism. Since the 1990s several groups have observed the emergence ofHaemophilus influenzaetype a (Hia), especially in indigenous communities in the northern regions of Canada and Alaska, to a stage where a solution is warranted to prevent further unnecessary deaths due to this pathogen. A glycoconjugate vaccine solution based upon the type a capsular polysaccharide (CPS) was investigated pre-clinically in an effort to illustrate the proof of concept for this approach. In this study we describe the growth of Hia and the isolation, purification and conjugation of the CPS to several carrier proteins. The resulting glycoconjugates were immunised in mice and rabbits provoking sera that facilitated bactericidal killing against all type a strains that we tested. This study has illustrated the pre-clinical proof of concept of a glycoconjugate vaccine based on the CPS of Hia asa solution to this emerging disease.
PubMed ID
28951087 View in PubMed
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