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Pilin gene variation in Neisseria gonorrhoeae: reassessing the old paradigms.

ABSTRACT: Neisseria gonorrhoeae displays considerable potential for antigenic variation as shown in human experimental studies. Various surface antigens can change either by antigenic variation using RecA-dependent recombination schemes (e.g. PilE antigenic variation) or, alternatively, through phase variation (on/off switching) in a RecA-independent fashion (e.g. Opa and lipooligosaccharide phase variation). PilE antigenic variation has been well documented over the years. However, with the availability of the N. gonorrhoeae FA1090 genome sequence, considerable genetic advances have recently been made regarding the mechanistic considerations of the gene conversion event, leading to an altered PilE protein. This review will compare the various models that have been presented and will highlight potential mechanistic problems that may constrain any genetic model for pilE gene variation.

SUBMITTER: Hill SA

PROVIDER: S-EPMC2753986 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Pilin gene variation in Neisseria gonorrhoeae: reassessing the old paradigms.

Hill Stuart A SA Davies John K JK

FEMS microbiology reviews 20090501 3

Neisseria gonorrhoeae displays considerable potential for antigenic variation as shown in human experimental studies. Various surface antigens can change either by antigenic variation using RecA-dependent recombination schemes (e.g. PilE antigenic variation) or, alternatively, through phase variation (on/off switching) in a RecA-independent fashion (e.g. Opa and lipooligosaccharide phase variation). PilE antigenic variation has been well documented over the years. However, with the availability ...[more]

PMID: 19396954

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Project description:The obligate human pathogen Neisseria gonorrhoeae is the sole aetiologic agent of the sexually transmitted infection, gonorrhea. Required for gonococcal infection, Type IV pili (Tfp) mediate many functions including adherence, twitching motility, defense against neutrophil killing, and natural transformation. Critical for immune escape, the gonococcal Tfp undergoes antigenic variation, a recombination event at the pilE locus that varies the surface exposed residues of the major pilus subunit PilE (pilin) in the pilus fiber. This programmed recombination system has the potential to produce thousands of pilin variants and can produce strains with unproductive pilin molecules that are completely unable to form Tfp. Saturating mutagenesis of the 3' third of the pilE gene identified 68 unique single nucleotide mutations that each resulted in an underpiliated colony morphology. Notably, all isolates, including those with undetectable levels of pilin protein and no observable surface-exposed pili, retained an intermediate level of transformation competence not exhibited in ΔpilE strains. Site-directed, nonsense mutations revealed that only the first 38 amino acids of the mature pilin N-terminus (the N-terminal domain or Ntd) are required for transformation competence, and microscopy, ELISAs and pilus purification demonstrate that extended Tfp are not required for competence. Transformation in strains producing only the pilin Ntd has the same genetic determinants as wild-type transformation. The Ntd corresponds to the alternative product of S-pilin cleavage, a specific proteolysis unique to pathogenic Neisseria. Mutation of the S-pilin cleavage site demonstrated that S-pilin cleavage mediated release of the Ntd is required for competence when a strain produces unproductive pilin molecules that cannot assemble into a Tfp through mutation or antigenic variation. We conclude that S-pilin cleavage evolved as a mechanism to maintain competence in nonpiliated antigenic variants and suggest there are alternate forms of the Tfp assembly apparatus that mediate various functions including transformation.

Dataset Information

Pilin gene variation in Neisseria gonorrhoeae: reassessing the old paradigms.

Publications

Pilin gene variation in Neisseria gonorrhoeae: reassessing the old paradigms.

Similar Datasets

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