The Pathology of Gonorrh a

Harkness, A. H.

doi:10.1136/sti.24.4.137

Cited by 56 publications

(68 citation statements)

References 5 publications

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“…Harkness (22) reviewed data showing that in patients with acute gonorrhea, gonococci had penetrated the mucosal surface and were multiplying in the subepithelial space by day 3 of infection. However, it is unclear whether squamous cells of the cervix are truly invaded by gonococci (12).…”

Section: Mucosal Invasionmentioning

confidence: 99%

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Gonococcal and meningococcal pathogenesis as defined by human cell, cell culture, and organ culture assays

Stephens

1989

Clin Microbiol Rev

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Human cells, cell cultures, and organ cultures have been extremely useful for studying the events that occur when gonococci and meningococci encounter human mucosal surfaces. The specificity and selectivity of these events for human cells are striking and correlate with the adaptation of these pathogens for survival on human mucous membranes. To colonize these sites, meningococci and gonococci have developed mechanisms to damage local host defenses such as the mucociliary blanket, to attach to epithelial cells, and to invade these cells. Attachment to epithelial cells mediated by pili, and to some types of cells mediated by PIIs, serves to anchor the organism close to sources of nutrition and allows multiplication. Intracellular invasion, possibly initiated by the major porin protein, may provide additional nutritional support and protection from host defenses. Mucosal invasion may also result in access of gonococci and meningococci to the bloodstream, leading to dissemination.

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Section: Mucosal Invasionmentioning

confidence: 99%

“…Only studies of gonococcal urethritis in men (29,63) and testing of potential vaccine candidates have been possible. Human tissue specimens obtained from infected individuals has provided important information (12,14,22), but these specimens are limited in availability and are often obtained late in the course of infection.…”

mentioning

confidence: 99%

Gonococcal and meningococcal pathogenesis as defined by human cell, cell culture, and organ culture assays

Stephens

1989

Clin Microbiol Rev

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“…Harkness concluded, through clinical observations and light microscopic studies of tissue derived from patients naturally infected with gonococci, that N. gonorrhoeae was incapable of invading the stratified squamous epithelium of the ectocervix (22). He also concluded that progressive infection occurred as the result of colonization of the endocervical columnar epithelium with subsequent transmigration through the intercellular junctions to the subepithelial tissues or lymphatic vessels (22). Evans (11) performed electron microscopic examination of biopsies derived from the cervical squamocolumnar junction of patients infected with N. gonorrhoeae.…”

mentioning

confidence: 99%

Neisseria gonorrhoeaeElicits Membrane Ruffling and Cytoskeletal Rearrangements upon Infection of Primary Human Endocervical and Ectocervical Cells

Edwards¹,

Shao²,

Ault

et al. 2000

Infect Immun

121

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Neisseria gonorrhoeae is a strict human pathogen that is, primarily, transmitted by close sexual contact with an infected individual. Gonococcal infection of the male urogenital tract has been well studied in experimental human models and in urethral cell culture systems. Recent studies, using tissue culture cell systems, have suggested a role for the cervical epithelium in gonococcal infection of females; however, the nature of gonococcal infection of the normal uterine cervix remains controversial. To address this enigma, we have developed two primary human cervical epithelial cell systems from surgical biopsies. Gonococcal infection studies and electron microscopy show that N. gonorrhoeae is capable of infecting and invading both the endo-and the ectocervix. Invasion was found to occur primarily in an actin-dependent manner, but it does not appear to require de novo protein synthesis by either the bacterium or the host cervical cell. Membrane ruffles appear to be induced in response to gonococci. Consistent with membrane ruffling, gonococci were found residing within macropinosomes, and a concentrated accumulation of actin-associated proteins was observed to occur in response to gonococcal infection. Electron microscopy of clinically derived cervical biopsies show that lamellipodia formation and cytoskeletal changes, suggestive of membrane ruffles, also occur in the cervical epithelium of women with naturally acquired gonococcal cervicitis. These studies demonstrate the ability of N. gonorrhoeae to infect and invade both the endo-and the ectocervix of the normal uterine cervix. Gonococcal induced ruffling is a novel finding and may be unique to the cervical epithelium.

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confidence: 99%

“…Pilus retraction (27) then allows the colony opacity-associated (Opa) adhesins to confer a tight association between the bacteria and apically oriented host cellular receptors. These interactions facilitate bacterial entry into and transcellular transcytosis through epithelial cells and entry into the subepithelial compartment (11,21,26,45), presumably allowing the establishment of localized and/or disseminated infection (11,19).Neisserial Opa proteins are integral outer membrane proteins that are predicted to span the lipid bilayer eight times with four surface-exposed loops (24). Individual gonococcal strains possess ϳ11 different opa alleles, each of which may encode functionally and/or antigenically distinct variants (reviewed in reference 13).…”

mentioning

confidence: 99%

Engulfment ofNeisseria gonorrhoeae: Revealing Distinct Processes of Bacterial Entry by Individual Carcinoembryonic Antigen-Related Cellular Adhesion Molecule Family Receptors

2004

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Individual Neisseria gonorrhoeae colony opacity-associated (Opa) protein variants can bind up to four different carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) receptors. Most human cells encountered by gonococci express a combination of CEACAM receptors, thereby complicating the elucidation of intracellular signaling pathways triggered by individual receptors. Here, we compare the process of bacterial engulfment by a panel of stably transfected HeLa epithelial cell lines expressing each CEACAM receptor in isolation. CEACAM1 and CEACAM3 each contain proteinaceous transmembrane and cytoplasmic domains; however, the processes of neisserial uptake mediated by these receptors differ with respect to their susceptibilities to both tyrosine kinase inhibitors and the actin microfilament-disrupting agent cytochalasin D. Neisserial uptake mediated by glycosylphosphatidylinositol (GPI)-anchored CEACAM5 and CEACAM6 was not significantly affected by any of a broad spectrum of inhibitors tested. However, cleavage of the GPI anchor by phosphatidylinositol-specific phospholipase C reduced bacterial uptake by HeLa cells expressing CEACAM5, consistent with a single zipper-like mechanism of uptake mediated by this receptor. Regardless of the CEACAM receptor expressed, internalized gonococci were effectively killed by a microtubule-dependent process that required acidification of the bacterium-containing phagosome. Given the phase-variable nature of neisserial Opa proteins, these results indicate that the mechanism of bacterial engulfment and the cellular response to gonococcal infection depend on both the receptor specificities of the neisserial Opa protein variants expressed and the spectrum of CEACAM receptors present on target cells, each of which determines the combination of receptors ultimately engaged.Despite the existence of effective antibiotic therapy to clear the bacterium, recent estimates indicate that ϳ62 million new Neisseria gonorrhoeae infections occur each year (46). Infection likely begins with attachment of the gonococcal type IV pilus to the apical surface of mucosal epithelial cells (26,43). Pilus retraction (27) then allows the colony opacity-associated (Opa) adhesins to confer a tight association between the bacteria and apically oriented host cellular receptors. These interactions facilitate bacterial entry into and transcellular transcytosis through epithelial cells and entry into the subepithelial compartment (11,21,26,45), presumably allowing the establishment of localized and/or disseminated infection (11,19).Neisserial Opa proteins are integral outer membrane proteins that are predicted to span the lipid bilayer eight times with four surface-exposed loops (24). Individual gonococcal strains possess ϳ11 different opa alleles, each of which may encode functionally and/or antigenically distinct variants (reviewed in reference 13). The expression of each allele is phase variable due to frequent RecA-independent DNA rearrangements occurring within a pentanucleotide repeat sequence pres...

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The Pathology of Gonorrh a

Cited by 56 publications

References 5 publications

Gonococcal and meningococcal pathogenesis as defined by human cell, cell culture, and organ culture assays

Gonococcal and meningococcal pathogenesis as defined by human cell, cell culture, and organ culture assays

Neisseria gonorrhoeaeElicits Membrane Ruffling and Cytoskeletal Rearrangements upon Infection of Primary Human Endocervical and Ectocervical Cells

Engulfment ofNeisseria gonorrhoeae: Revealing Distinct Processes of Bacterial Entry by Individual Carcinoembryonic Antigen-Related Cellular Adhesion Molecule Family Receptors

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