Inter-strain homology of pilin gene sequences in Neisseria meningitidis isolates that express markedly different antigenic pilus types

Perry, Anthony C.F.; Nicolson, I. J.; Heckels, John E.; Saunders, J. R.

doi:10.1007/978-94-009-1383-7_49

Cited by 7 publications

(22 citation statements)

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“…Irreversible pilus phase variation in N. gonorrhoeae results from deletions at the full genomic complement of (one or two) pilE loci (12,14,23). Chromosomal deletions that may be analogous have also been observed for N. meningitidis in association with piliated-to-nonpiliated phase transition (17). Reversible gonococcal pilus phase variation apparently follows partial pilin gene replacement at pilE, and a similar mechanism may operate in pilus antigenic variation (30).…”

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“…Several meningococcal components have been implicated in pathogenesis, including filamentous protein appendages, called pili, that can be expressed both in laboratory culture and during natural infection (26,32). Meningococcal pili exhibit interstrain differences with respect to the physical and immunological properties of their structural subunit, pilin (17,32,34). In these and certain other respects, pilus expression in N. meningitidis and Neisseria gonorrhoeae is similar.…”

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“…In these and certain other respects, pilus expression in N. meningitidis and Neisseria gonorrhoeae is similar. The pili of both organisms promote attachment to human epithelia, and pilus expression in each case can be attenuated (an example of pilus phase variation), or an immunologically novel pilus type can be elaborated (pilus antigenic variation) (2, 5,9,17,23,31,33,36). Although gonococcal pilus phase variation can be either reversible or irreversible, it is not known whether the same applies in N. meningitidis.…”

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Neisseria meningitidis C114 contains silent, truncated pilin genes that are homologous to Neisseria gonorrhoeae pil sequences

1988

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Neisseria meningitidis pili can be classified into two groups: those (referred to here as class I pili) which are similar to gonococcal pili in that they react with monoclonal antibody SM1 and those that are dissimilar to gonococcal pili in that they lack the SM1-reactive epitope (class II pili). Pilus expression in N. meningitidis C114, a class II pilus-producing isolate, was investigated. The sole genomic segment of this strain that bore extensive homology with the pilE locus of Neisseria gonorrhoeae P9 was cloned in Escherichia coli. The production of the pilus structural subunit (pilin) from this meningococcal segment could not be detected by immunological and coupled in vitro transcription-translation analyses. Nucleotide sequence analysis revealed the presence in the C114 genome of two variant, tandemly arranged pilin genes (copies 1 and 2). Copies 1 and 2 are partial pilin genes that constitute part of a silent meningococcal pilin gene (pil gene) region, designated pilS. Both copies are truncated, corresponding to variable domains of the gonococcal pilE gene but lacking homologous N-terminal coding sequences. Located within sequences surrounding copies 1 and 2 were several classes of repeated elements that are associated with pil loci in N. gonorrhoeae.

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Neisseria meningitidis C114 contains silent, truncated pilin genes that are homologous to Neisseria gonorrhoeae pil sequences

1988

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“…Structural variation of pili arises predominantly from recombination events between silent and expressed pilin gene sequences. Strains of N. meningitidis produce one of two types of pili, which have been termed class I and II (Perry et al, 1987). The vast majority of isolates possess class I pili, which are structurally similar to those produced by N. gonorrhoeae and carry a pilE gene sequence highly homologous to the gonococcal pilE gene (Olafson et al, 1985;Perry et al, 1988;Potts and Saunders, 1988;Virji et al, 1989).…”

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Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria

Källström

Liszewski

Atkinson

et al. 1997

Molecular Microbiology

329

230

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SummaryPili of Neisseria gonorrhoeae and Neisseria meningitidis mediate binding of the bacteria to human cellsurface receptors. We found that purified pili bound to a 55-to 60-kDa doublet band on SDS-PAGE of separated human epithelial cell extracts. This is a migration pattern typical of membrane cofactor protein (MCP or CD46). MCP is a widely distributed human complement regulatory protein. Attachment of the bacteria to epithelial cells was blocked by polyclonal and monoclonal antibodies directed against MCP, suggesting that this complement regulator is a receptor for piliated Neisseria. We proved this hypothesis by demonstrating that piliated, but not non-piliated, gonococci bound to CHO cells transfected with human MCP-cDNA. We also demonstrated a direct interaction between purified recombinant MCP and piliated Neisseria. Finally, recombinant MCP protein produced in E. coli inhibited attachment of the bacteria to target cells. Taken together, our data show that MCP is a human cell-surface receptor for piliated pathogenic Neisseria.

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“…Many strains produce pilins which closely resemble gonococcal pilins in apparent M, and reactivity with mAbs SMl and SM2 , in possessing strong homology at the amino acid sequence level (Potts & Saunders, 1988) and in undergoing antigenic variation during infection (Tinsley & Heckels, 1986). Other strains produce pilins that fail to react with either mAb but react with polyclonal antisera raised against gonococcal pili to reveal pilins with apparent M , in the range 13000-16000 Perry et al, 1987a). These two types of meningococcal pili have been given a variety of designations by different authors, namely group 1 and group 2 , SMl-reactive and SM2-nonreactive (Achtman et al, 1988) and class I and class I1 (Perry et al, 1988); the last has subsequently been adopted as the recognized nomenclature (Hitchcock, 1989).…”

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confidence: 99%

Identification of Epitopes Recognized by Monoclonal Antibodies SM1 and SM2 Which React with All Pili of Neisseria gonorrhoeae but Which Differentiate between Two Structural Classes of Pili Expressed by Neisseria meningitidis and the Distribution of Their Encoding Sequences in the Genomes of Neisseria spp.

Virji

Heckels²,

Potts³

et al. 1989

Microbiology

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The pili expressed by all isolates of Neisseria gonorrhoeae react with two monoclonal antibodies, SM1 and SM2. In contrast, although many isolates of Neisseria meningitidis also express pili (class I) which react with antibodies SM1 and SM2, a proportion express pili (class 11) which fail to react. In order to define the epitopes recognized by these antibodies, a series of overlapping peptides corresponding to the amino acid sequence of conserved regions of gonococcal pili have been synthesized. The minimum epitope recognized by antibody SM1 was found to comprise a linear peptide EYYLN, corresponding to residues 49-53 of mature pilin. In contrast, antibody SM2 reacted with a number of peptides from around the cysteine residue (Cys 1) at position 120, suggesting that an extended region may contribute to a conformational epitope recognized by this antibody in the native protein. The identification of the two epitopes defines structural differences between the classes of pili expessed by meningococci. In order to determine the distribution of pilin gene sequences in Neisseria we used as hybridization probes an oligonucleotide (PS 1) with the sequence 5'-GAGTATTACCTGAATCA-3' which spans the coding region for the SMl epitope, and a fragment of the 3' end of the gonococcal pilE gene which contains conserved sequences flanking the two Cys codons and encodes the SM2 epitope. All strains of N . gonorrhoeae and N. meningitidis tested, regardless of piliation phenotype, harboured DNA sequences homologous to those encoding the carboxy-terminus of meningococcal class I pilin. Furthermore, all gonococci and all meningocococci producing class I pili hybridized with oligonucleotide probe PS 1. Non-reverting non-piliated derivatives of previously class I pilus-producing strains showed reduced hybridization signals with this probe, but nevertheless retained sequences homologous to the coding sequence for the SMl epitope. However, meningococci producing class I1 pili could be divided into two groups on the basis of their reaction with the PS1 probe: half the strains tested failed to react, which is consistent with our previous analysis of silent class I pilin sequences; the remainder reacted (relatively weakly) with the probe, suggesting that the silentpil sequences in these strains extend further towards the 5' end of the pilin gene than in strains studied previously. Some strains of Neisseria lactarnica reacted weakly with both types of probe but failed to produce SM1-reactive pili. In contrast,

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Inter-strain homology of pilin gene sequences in Neisseria meningitidis isolates that express markedly different antigenic pilus types

Cited by 7 publications

References 4 publications

Neisseria meningitidis C114 contains silent, truncated pilin genes that are homologous to Neisseria gonorrhoeae pil sequences

Neisseria meningitidis C114 contains silent, truncated pilin genes that are homologous to Neisseria gonorrhoeae pil sequences

Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria

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