Neisseria gonorrhoeae Recombinant Strains Expressing Hybrid Serological Reactivities of Outer Membrane Proteins IA and IB

Abstract

The inheritance of epitopes of protein I, the principal protein of the outer membrane of Neisseria gonorrhoeae, was investigated by DNA-mediated transformation. Protein I transformants were isolated by selection for the linked spectinomycin-resistance determinant. Twelve monoclonal antibodies used in coagglutination tests identified epitopes of the two forms of protein I (P.IA and P.IB). A given gonococcal culture from patients expresses epitopes of either P.IA or P.IB and rarely, if ever, exhibits hybrid P.IA/P.IB reactivities. Nevertheless, we found 35 P.IA/P.IB recombinants among 1506 transformants. Transmission by DNA of the hybrid reactivities and the apparent molecular mass characteristic of a given P.IA/P.IB species verified the genetic basis of the phenotypic changes. A recombinant that expressed six P.IA and two P.IB epitopes is of interest as a possible component of a gonococcal vaccine, because one or more of these epitopes are shared with 99.8% of a worldwide collection of 1858 clinical strains.

Naturally occurring isolates ofNeisseria gonorrhoea, which display anomalous serovar properties, express PIA/PIB hybrid porins, deletions in PIB or novel PIA molecules

“…Given the known ability of gonococci to be transformed by DNA from other strains and the likely occurrence of double infection by PIA and PIB expressing strains, it is surprising that occurrence of genuine PIA/PIB hybrids has not been previously documented. Such strains have also been constructed in vitro by transformation with chromosomal DNA [12] and by recombinant DNA methods with cloned por genes [18]. The rarity of naturally occurring hybrids suggests that such strains must suffer a selective disadvantage in vivo.…”

“…Although hybrids between PIA and PIB have been constructed in vitro [11, 12], the vast majority of clinical isolates react with either PIA or PIB antibodies, confirming that only one allele of the por gene is being expressed [13]. However a recent study described two clusters of gonococcal isolates which reacted with antibodies to both PIA and PIB and hence appeared to express a hybrid porin [14].…”

Naturally occurring isolates of Neisseria gonorrhoea, which display anomalous serovar properties, express PIA/PIB hybrid porins, deletions in PIB or novel PIA molecules

“…Such strains have also been constructed in vitro by transformation with chromosomal DNA [12] and by recombinant DNA methods with cloned por genes [18]. The rarity of naturally occurring hybrids suggests that such strains must su¡er a selective disadvantage in vivo.…”

“…Given the known ability of gonococci to be transformed by DNA from other strains and the likely occurrence of double infection by PIA and PIB expressing strains, it is surprising that occurrence of genuine PIA/PIB hybrids has not been previously documented. Such strains have also been constructed in vitro by transformation with chromosomal DNA [12] and by recombinant DNA methods with cloned por genes [18]. The rarity of naturally occurring hybrids suggests that such strains must su¡er a selective disadvantage in vivo.…”

“…Although hybrids between PIA and PIB have been constructed in vitro [11,12], the vast majority of clinical isolates react with either PIA or PIB antibodies, con¢rming that only one allele of the por gene is being expressed [13]. However a recent study described two clusters of gonococcal isolates which reacted with antibodies to both PIA and PIB and hence appeared to express a hybrid porin [14].…”