Multiple gonococcal pilin antigenic variants are produced during experimental human infections.

Seifert, H. Steven; Wright, C J; Jerse, Ann E.; Cohen, Myron S.; Cannon, Janne G.

doi:10.1172/jci117290

Cited by 157 publications

(169 citation statements)

References 30 publications

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“…In vitro cell culture and primary cell-based systems have clearly established that most Opa variants can bind one or more human CEACAMs, and transgenic mouse-based studies corroborate the importance of this binding for the establishment of infection (37,38). Experimental human urethral model studies also suggest the importance of Opa proteins and pilus (6,(12)(13)(14)(65)(66)(67), yet the binding specificity of Opa variants expressed during human infection had not been addressed before this study.…”

Section: Discussionmentioning

confidence: 96%

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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Section: Discussionmentioning

confidence: 96%

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

et al. 2015

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“…It is possible that the further study of (Istock et al, 1992) and to a lesser extent N . meningitidis (Caugant et al, 1987;Maynard Smith et al, 1993), exhibit frequent extensive recombination and data suggests that this can occur in vivo (Seifert et al, 1994). However, statistical analysis of the MEE data presented indicates significant linkage disequilibrium, suggesting that although the potential for genetic exchange exists in H .…”

Section: Genetic Variation In Relation To Disease Typementioning

confidence: 93%

Differences in genetic diversity of nonecapsulated Haemophilus influenzae from various diseases

Alphen

Caugant²,

Duim

et al. 1997

Microbiology

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Genetic relationships among 80 isolates of nonencapsulated Haemophilus influenzae recovered from different disease types were determined by multilocus enzyme electrophoresis (MEE) a t 13 enzyme loci in an attempt to assess the association between multilocus genotype and disease. The isolates were obtained from 15 patients with meningitis, 10 with otitis media, I 9 with chronic bronchitis, 20 with cystic fibrosis, and 16 were obtained from healthy carriers. The 80 isolates were assigned to 69 electrophoretic types (ETs) falling into 5 groups. Isolates from each disease entity were represented by a variety of genotypes; however, cluster analysis from a matrix of genetic distances between ETs revealed that the ETs of the otitis media and meningitis isolates were all clustered within a genetic distance of 055 (group I). In addition, no genotypes were shared between H. influenzae carrier isolates and isolates from cases of disease. H. influenzae isolates from healthy individuals were distributed significantly differently from those from chronic bronchitis meningitis and otitis media patients. The genetic diversity (H) of carrier strains was greatest, although not statistically different from that of isolates from patients with disease. It was concluded that the genetic distribution of acute disease isolates is not random over the five ET groups, although the genetic diversity within the groups is not different. The effect of bacterial persistence in the host on the genetic diversity of H. influenzae is discussed.

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“…3 (Difco), 0n4% K # HPO % (Fisher), 0n1% KH # PO % (Fisher), 0n1 % NaCl (Fisher)] with Kellogg Supplements and 0n042 % sodium bicarbonate (Sigma) at 37 mC with rotation. All gonococcal strains used in this study were derivatives of strain FA1090 1-81-S2 with matched pilE sequences (Seifert et al, 1994) determined as described by Stohl & Seifert (2001 (Seifert, 1997). In Gc, constructs are carried in either the Gc recA or the Cg8 locus, as indicated.…”

Section: Methodsmentioning

confidence: 99%

Differential cross-complementation patterns of Escherichia coli and Neisseria gonorrhoeae RecA proteins

2002

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The Escherichia coli RecA protein is one of the best-studied enzymes, but less is understood about how RecA homologues of other species are similar to or different from the E. coli RecA. In the Gram-negative pathogen Neisseria gonorrhoeae (the gonococcus ; Gc), the causative agent of gonorrhoea, RecA is involved in DNA transformation, pilin antigenic variation, and DNA repair. By expressing the recA genes from Gc and E. coli under control of lac regulatory sequences in E. coli, the authors have shown that the Gc RecA fully complements an E. coli recA mutant for homologous recombination, but only partially complements for survival to DNA damage. By expressing similar constructs in Gc, it was shown that the E. coli RecA complements for pilin antigenic variation, partially complements for DNA transformation, but does not complement for survival to DNA damage, suggesting that species-specific interactions are important for DNA repair, but not for homologous recombination. Co-expression of the E. coli recA and recX genes in Gc suggests that in this heterologous system RecX modulates RecA-mediated processes.

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Multiple gonococcal pilin antigenic variants are produced during experimental human infections.

Cited by 157 publications

References 30 publications

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

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

Differences in genetic diversity of nonecapsulated Haemophilus influenzae from various diseases

Differential cross-complementation patterns of Escherichia coli and Neisseria gonorrhoeae RecA proteins

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