ABSTRACTNeisseria meningitidis, one of the major causes of bacterial meningitis and sepsis, is a member of the genusNeisseria, which includes species that colonize the mucosae of many animals. Three meningococcal proteins, factor H-binding protein (fHbp), neisserial heparin-binding antigen (NHBA), andN. meningitidisadhesin A (NadA), have been described as antigens protective againstN. meningitidisof 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 genusNeisseria, 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 fromN. cinereawas introduced intoN. meningitidisby 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.IMPORTANCEThe upper respiratory tract of healthy individuals is a complex ecosystem colonized by many bacterial species. Among these, there are representatives of the genusNeisseria, includingNeisseria meningitidis, a major cause of bacterial meningitis and sepsis. Given the close relationship between commensal and pathogenic species, a protein-based vaccine againstN. meningitidishas the potential to impact the other commensal species ofNeisseria. 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.
Colistin Sensitivity and Factor H-Binding Protein Expression among Commensal
Neisseria
Species
