Conservation of Meningococcal Antigens in the Genus <italic toggle="yes">Neisseria</italic>

ABSTRACT Neisseria meningitidis, one of the major causes of bacterial meningitis and sepsis, is a member of the genus Neisseria, which includes species that colonize the mucosae of many animals. Three meningococcal proteins, factor H-binding protein (fHbp), neisserial heparin-binding antigen (NHBA),...

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Autores principales:	Alessandro Muzzi, Marirosa Mora, Mariagrazia Pizza, Rino Rappuoli, Claudio Donati
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/276f00afc56843df903ae95670a553b0
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spelling	oai:doaj.org-article:276f00afc56843df903ae95670a553b02021-11-15T15:40:06ZConservation of Meningococcal Antigens in the Genus <italic toggle="yes">Neisseria</italic>10.1128/mBio.00163-132150-7511https://doaj.org/article/276f00afc56843df903ae95670a553b02013-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00163-13https://doaj.org/toc/2150-7511ABSTRACT Neisseria meningitidis, one of the major causes of bacterial meningitis and sepsis, is a member of the genus Neisseria, which includes species that colonize the mucosae of many animals. Three meningococcal proteins, factor H-binding protein (fHbp), neisserial heparin-binding antigen (NHBA), and N. meningitidis adhesin A (NadA), have been described as antigens protective against N. meningitidis of serogroup B, and they have been employed as vaccine components in preclinical and clinical studies. In the vaccine formulation, fHbp and NHBA were fused to the GNA2091 and GNA1030 proteins, respectively, to enhance protein stability and immunogenicity. To determine the possible impact of vaccination on commensal neisseriae, we determined the presence, distribution, and conservation of these antigens in the available genome sequences of the genus Neisseria, finding that fHbp, NHBA, and NadA were conserved only in species colonizing humans, while GNA1030 and GNA2091 were conserved in many human and nonhuman neisseriae. Sequence analysis showed that homologous recombination contributed to shape the evolution and distribution of both NHBA and fHbp, three major variants of which have been defined. fHbp variant 3 was probably the ancestral form of meningococcal fHbp, while fHbp variant 1 from N. cinerea was introduced into N. meningitidis by a recombination event. fHbp variant 2 was the result of a recombination event inserting a stretch of 483 bp from variant 1 into the variant 3 background. These data indicate that a high rate of exchange of genetic material between neisseriae that colonize the human upper respiratory tract exists. IMPORTANCE The upper respiratory tract of healthy individuals is a complex ecosystem colonized by many bacterial species. Among these, there are representatives of the genus Neisseria, including Neisseria meningitidis, a major cause of bacterial meningitis and sepsis. Given the close relationship between commensal and pathogenic species, a protein-based vaccine against N. meningitidis has the potential to impact the other commensal species of Neisseria. For this reason, we have studied the distribution and evolutionary history of the antigen components of a recombinant vaccine, 4CMenB, that recently received approval in Europe under the commercial name of Bexsero®. We found that fHbp, NHBA, and NadA can be found in some of the human commensal species and that the evolution of these antigens has been essentially shaped by the high rate of genetic exchange that occurs between strains of neisseriae that cocolonize the same environment.Alessandro MuzziMarirosa MoraMariagrazia PizzaRino RappuoliClaudio DonatiAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 3 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Alessandro Muzzi Marirosa Mora Mariagrazia Pizza Rino Rappuoli Claudio Donati Conservation of Meningococcal Antigens in the Genus <italic toggle="yes">Neisseria</italic>
description	ABSTRACT Neisseria meningitidis, one of the major causes of bacterial meningitis and sepsis, is a member of the genus Neisseria, which includes species that colonize the mucosae of many animals. Three meningococcal proteins, factor H-binding protein (fHbp), neisserial heparin-binding antigen (NHBA), and N. meningitidis adhesin A (NadA), have been described as antigens protective against N. meningitidis of serogroup B, and they have been employed as vaccine components in preclinical and clinical studies. In the vaccine formulation, fHbp and NHBA were fused to the GNA2091 and GNA1030 proteins, respectively, to enhance protein stability and immunogenicity. To determine the possible impact of vaccination on commensal neisseriae, we determined the presence, distribution, and conservation of these antigens in the available genome sequences of the genus Neisseria, finding that fHbp, NHBA, and NadA were conserved only in species colonizing humans, while GNA1030 and GNA2091 were conserved in many human and nonhuman neisseriae. Sequence analysis showed that homologous recombination contributed to shape the evolution and distribution of both NHBA and fHbp, three major variants of which have been defined. fHbp variant 3 was probably the ancestral form of meningococcal fHbp, while fHbp variant 1 from N. cinerea was introduced into N. meningitidis by a recombination event. fHbp variant 2 was the result of a recombination event inserting a stretch of 483 bp from variant 1 into the variant 3 background. These data indicate that a high rate of exchange of genetic material between neisseriae that colonize the human upper respiratory tract exists. IMPORTANCE The upper respiratory tract of healthy individuals is a complex ecosystem colonized by many bacterial species. Among these, there are representatives of the genus Neisseria, including Neisseria meningitidis, a major cause of bacterial meningitis and sepsis. Given the close relationship between commensal and pathogenic species, a protein-based vaccine against N. meningitidis has the potential to impact the other commensal species of Neisseria. For this reason, we have studied the distribution and evolutionary history of the antigen components of a recombinant vaccine, 4CMenB, that recently received approval in Europe under the commercial name of Bexsero®. We found that fHbp, NHBA, and NadA can be found in some of the human commensal species and that the evolution of these antigens has been essentially shaped by the high rate of genetic exchange that occurs between strains of neisseriae that cocolonize the same environment.
format	article
author	Alessandro Muzzi Marirosa Mora Mariagrazia Pizza Rino Rappuoli Claudio Donati
author_facet	Alessandro Muzzi Marirosa Mora Mariagrazia Pizza Rino Rappuoli Claudio Donati
author_sort	Alessandro Muzzi
title	Conservation of Meningococcal Antigens in the Genus <italic toggle="yes">Neisseria</italic>
title_short	Conservation of Meningococcal Antigens in the Genus <italic toggle="yes">Neisseria</italic>
title_full	Conservation of Meningococcal Antigens in the Genus <italic toggle="yes">Neisseria</italic>
title_fullStr	Conservation of Meningococcal Antigens in the Genus <italic toggle="yes">Neisseria</italic>
title_full_unstemmed	Conservation of Meningococcal Antigens in the Genus <italic toggle="yes">Neisseria</italic>
title_sort	conservation of meningococcal antigens in the genus <italic toggle="yes">neisseria</italic>
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/276f00afc56843df903ae95670a553b0
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Conservation of Meningococcal Antigens in the Genus <italic toggle="yes">Neisseria</italic>

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