Neisseria meningitidis causes meningitis and/or septicaemia in children and young adults resulting in considerable morbidity and mortality. Searching of NCBI databases with the term “Factor H binding protein, Neisseria meningitidis” identified two proteins important in N. meningitidis biology: Neisseria surface protein A (nspA) and the porin B (porB). Predicted protein domains of Factor H binding protein, nspA and porB were retrieved following blastp searches. In contrast, searching of NCBI databases with “lnt and Neisseria meningitidis MC58” retrieved no additional proteins although predicted protein domains of lnt were retrieved.
Neisseria meningitidis is a pathogenic species of bacteria which causes meningitis and/or septicaemia in children and young adults. It is responsible for both sporadic cases of meningitis and epidemics of the disease worldwide, producing considerable morbidity and mortality (Rouphael and Stephens, 2012). N. meningitides is a -proteobacteria with the taxonomic lineage of: Bacteria; Proteobacteria; Betaproteobacteria; Neisseriales; Neisseriaceae; Neisseria (NCBI Taxonomy Browser, 2015). The majority of N. meningitidis strains which cause disease are classified as serogroup A, B or C, with the expression of specific capsular polysaccharides determining the serogroup type (Rouphael and Stephens, 2012; Wellcome Trust Sanger Institute, 2015). Strains of N. meningitides which cause epidemics in developing countries are generally typed as serogroup A, whereas serogroup B and C strains cause meningitis outbreaks in the developed world (Wellcome Trust Sanger Institute, 2015). Immunological immunoreactivity of N. meningitidis strains has identified a further three serogroups (W-135, X and Y) in addition to serogroups A, B and C which cause life threatening disease (Rouphael and Stephens, 2012). A quadrivalent meningococcal conjugate vaccine against serogroups A, C, Y and W-135 has been developed which is recommended in the USA for young children (Rouphael and Stephens, 2012).
The complete nucleotide sequence of a number of N. meningitis strains have been determined with the serogroup A strain Z2491 (Parkhill et al., 2000) and the serogroup B strain MC58 (Tettelin et al., 2000) being the first to be completely sequenced. Sequencing of N. meningitis strain Z2491 determined that the genome was 2,184,406 base pairs in length, with a predicted 2,121 coding sequences; and the genome of the serogroup B strain MC58 was sized 2,272,351 base pairs with a predicted 2,158 coding sequences (Parkhill et al., 2000; Tettelin et al., 2000). Of the 2,158 predicted coding sequences in strain MC58, just over half of them (1,158, 53.7%) were assigned a biological function (Tettelin et al., 2000). The genome sequence of several other N. meningitides strains have been determined (Rouphael and Stephens, 2012) including the serogroup B strain H44/76 (Piet et al., 2011) and show that the N. meningitides genome is about 2.0 – 2.2 megabases in length, containing around 2,000 genes (Rouphael and Stephens, 2012).
In common with other Gram negative bacteria, the gross structure of the subcapsular cell envelope of N. meningitidis comprises an outer membrane, a peptidoglycan layer between the two cell membranes known as the periplasmic space, and an inner or cytoplasmic membrane (Rouphael and Stephens, 2012).
Two serogroup B vaccines which have recently been developed against N. meningitidis contain factor H binding protein (Giuntini et al., 2015). Searches of NCBI databases using this term were conducted in order to determine information regarding the biology of this protein. A second search was done using lnt apolipoprotein N-acyltransferase which acrylates membrane lipoproteins.
The initial search of all NCBI databases (url: http://www.ncbi.nlm.nih.gov/gquery/) was with the term “Factor H binding protein, Neisseria meningitidis”. This identified two genes which were explored further.
A search of the NCBI Protein database (url: http://www.ncbi.nlm.nih.gov/protein/) retrieved the protein accession number which was used to identify proteins with related amino acid sequences using blastp (Altschul et al., 1997) from the NCBI BLAST website (url: http://blast.ncbi.nlm.nih.gov/Blast.cgi?CMD=Web&PAGE_TYPE=BlastHome). Blastp also provided information on conserved domain database (CDD) analysis of the query protein sequence (Marchler-Bauer et al. 2015).
A search of all NCBI databases with “Factor H binding protein, Neisseria meningitidis” retrieved a number of entries including two from NCBI Gene with a match to N. meningitidis genes: nspA outer membrane protein [ Neisseria meningitidis MC58 ] (NCBI Gene, 2015a); and porB major outer membrane protein PIB [ Neisseria meningitidis MC58 ] (NCBI Gene, 2015b).
Neisserial surface protein A (nspA)
A search of the NCBI Protein database with Nspa retrieved its accession number, NP_273705 and showed that the protein comprised 174 amino acids (NCBI Protein, 2015a). Following a blastp search of non-redundant (nr) protein sequences several conserved domains were identified on Nspa (Figure 1). This included a specific hit with the Opacity (accession number pfam02462) family porin protein domain which mediate a range of interactions between the pathogen and host cells (NCBI Conserved Protein Domain Family, 2015a). Non specific hits against the LomR domain – Opacity protein and related surface antigens, and the gram_neg_porins domain (see porB below) were also identified.