Opacity genes in Neisseria gonorrhoeae: Control of phase and antigenic variation

Stern, Anne; Brown, Melissa A.; Nickel, Peter; Meyer, Thomas F.

doi:10.1016/0092-8674(86)90366-1

Cited by 416 publications

(337 citation statements)

References 31 publications

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“…Expression of Opa (opacity) outer membrane proteins is variable as a result of slipped-strand mispairing changing the number of pentanucleotide repeats within the signal peptide region of opa alleles (Stern et al, 1986;Stern and Meyer, 1987;Murphy et al, 1989;Belland et al, 1997). In addition, extensive sequence differences that are most concentrated in two regions called HV1 and HV2 distinguish many opa alleles.…”

Section: Introductionmentioning

confidence: 99%

Clonal descent and microevolution of Neisseria meningitidis during 30 years of epidemic spread

Morelli

Malorny

Müller

et al. 1997

Molecular Microbiology

101

137

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SummarySerogroup A meningococci of subgroups III, IV-1 and IV-2 are probably descended from a common ancestor that existed in the nineteenth century. The 10.5 kb sequences spanning five distinct chromosomal loci, encoding cell-surface antigens, a secreted protease or housekeeping genes and intergenic regions, were almost identical in strains of those subgroups isolated in 1966, 1966 and 1917 respectively. During the subsequent two to three decades, all of these loci varied as a result of mutation, translocation or import of DNA from unrelated neisseriae. Thus, microevolution occurs frequently in naturally transformable bacteria. Many variants were isolated only once or within a single geographical location and disappeared thereafter. Other variants achieved genetic fixation within months or a few years. The speed with which sequence variation is either eliminated or fixed may reflect sequential bottlenecks associated with epidemic spread and contrasts with the results of phylogenetic analyses from bacteria that do not cause epidemics.

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Section: Introductionmentioning

confidence: 99%

Clonal descent and microevolution of Neisseria meningitidis during 30 years of epidemic spread

Morelli

Malorny

Müller

et al. 1997

Molecular Microbiology

101

137

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“…However, unlike Opc, Opa protein expression is regulated at the translational level (Stern et al, 1986;Kawula et al, 1988;Belland et al, 1989). Opa proteins are encoded by a family of opa genes scattered throughout the bacterial genome Bihlmaier et al, 1991), and vary dramatically in sequence, particularly at two cell-surface-exposed hypervariable regions (Connell et al, 1988;Aho et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Two‐dimensional structure of the Opc invasin from Neisseria meningitidis

Merker

Tommassen

Kušećek

et al. 1997

Molecular Microbiology

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SummaryA two-dimensional structural model was devised for the Opc outer membrane protein invasin which contains 10 transmembrane strands and five surfaceexposed loops. One continuous epitope recognized by three monoclonal antibodies was localized to the tip of loop 2 by synthetic peptides and site-directed mutagenesis while a second, discontinuous epitope recognized by a fourth antibody was localized to loops 4 and 5 by insertion mutagenesis. These monoclonal antibodies are bactericidal and inhibit adhesion and invasion. Most of the T-cell epitopes defined by Wiertz et al. (1996) were localized to the transmembrane strands. Oligonucleotides encoding a foreign epitope (ٌ) from Semliki Forest virus were inserted into Bgl II restriction sites created by site-directed mutagenesis. The ٌ epitopes inserted in all five predicted loops were recognized on the cell surface of live Escherichia coli bacteria by a monoclonal antibody and are exposed while ٌ epitopes in the N-terminus or three predicted turns were not. The results thus confirm important predictions of the model and define five permissive sites within surface-exposed loops which can be used to insert foreign epitopes.

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“…Each gonococcal isolate possesses ϳ11 different opa genes, each encoding antigenically and phenotypically distinct variants that reversibly turn expression "off" and "on" at a rate estimated to be 10 Ϫ3 to 10 Ϫ4 /cell/generation (10,11). N. gonorrhoeae isolates from both naturally infected men and women are predominantly Opa ϩ , as are isolates obtained from men experimentally infected with transparent (Opa phase-varied off) colonies (12)(13)(14).…”

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confidence: 99%

Selection for a CEACAM Receptor-Specific Binding Phenotype during Neisseria gonorrhoeae Infection of the Human Genital Tract

et al. 2015

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Infections by Neisseria gonorrhoeae are increasingly common, are often caused by antibiotic-resistant strains, and can result in serious and lasting sequelae, prompting the reemergence of gonococcal disease as a leading global health concern. N. gonorrhoeae is a human-restricted pathogen that primarily colonizes urogenital mucosal surfaces. Disease progression varies greatly between the sexes: men usually present with symptomatic infection characterized by a painful purulent urethral discharge, while in women, the infection is often asymptomatic, with the most severe pathology occurring when the bacteria ascend from the lower genital tract into the uterus and fallopian tubes. Classical clinical studies demonstrated that clinically infectious strains uniformly express Opa adhesins; however, their specificities were unknown at the time. While in vitro studies have since identified CEACAM proteins as the primary target of Opa proteins, the gonococcal specificity for this human family of receptors has not been addressed in the context of natural infection. In this study, we characterize a collection of low-passage-number clinicalspecimen-derived N. gonorrhoeae isolates for Opa expression and assess their CEACAM-binding profiles. We report marked in vivo selection for expression of phase-variable Opa proteins that bind CEACAM1 and CEACAM5 but selection against expression of Opa variants that bind to the neutrophil-restricted decoy receptor CEACAM3. This is the first study showing phenotypic selection for distinct CEACAM-binding phenotypes in vivo, and it supports the opposing functions of CEACAMs that facilitate infection versus driving inflammation within the genital tract.

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Opacity genes in Neisseria gonorrhoeae: Control of phase and antigenic variation

Cited by 416 publications

References 31 publications

Clonal descent and microevolution of Neisseria meningitidis during 30 years of epidemic spread

Clonal descent and microevolution of Neisseria meningitidis during 30 years of epidemic spread

Two‐dimensional structure of the Opc invasin from Neisseria meningitidis

Selection for a CEACAM Receptor-Specific Binding Phenotype during Neisseria gonorrhoeae Infection of the Human Genital Tract

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