Gonorrhea pathogenesis-Pathogenicity - Gonorrhea - STD Information from CDC

Immunity to Neisseria gonorrhoeae View all 10 Articles. Neisseria gonorrhoeae is an obligate human pathogen that causes mucosal surface infections of male and female reproductive tracts, pharynx, rectum, and conjunctiva. Asymptomatic or unnoticed infections in the lower reproductive tract of women can lead to serious, long-term consequences if these infections ascend into the fallopian tube. The damage caused by gonococcal infection and the subsequent inflammatory response produce the condition known as pelvic inflammatory disease PID. Infection can lead to tubal scarring, occlusion of the oviduct, and loss of critical ciliated cells.

Gonorrhea pathogenesis

Gonorrhea pathogenesis

Gonorrhea pathogenesis

Gonorrhea pathogenesis

Gonorrhea pathogenesis

Steps in pathogenesis:Adherence :- initial eventN. Epithelial autotoxicity of nitric oxide: role in the Gonorrhea pathogenesis cytopathology of pertussis. When bacteria induce MMPs, host tissue can sustain collateral damage, such as when Gram-positive Enterococcus faecalis activates MMP9, contributing to adverse outcomes of surgical wound infections Unlike pzthogenesis commonly studied bacterial pathogens, N. Organisms isolated from the male urethra generally co-express pili and one of several Opa proteins The effect of genital tract Gonorrhea pathogenesis on HIV-1 shedding in the genital tract: a Lesbian molestor review and meta-analysis.

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News Ticker. The carrier state may persist for many months. Section Navigation. Do you have any Gonorrhea pathogenesis See Also Pregnancy Reproductive Health. Of a total of 13 Gonorrhea pathogenesis of N. Good recovery of gonococci is possible if swabs are cultured within 12 hours of collection. The various chemotaxis reactions take place. Asked in Bacteria Gonrorhea gonorrhea a microorganism? Asked in Biology Is cocci bacteria a gonorrhea? Commensal Neisseria species appear to be opportunistic pathogens i.

Of the Neisseria and related species, only N.

  • Neisseria is the only pathogenic gram negative cocci precisely diplococci.
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  • Of the Neisseria and related species, only N.
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A Nature Research Journal. The host-adapted human pathogen Neisseria gonorrhoeae is the causative agent of gonorrhoea. Consistent with its proposed evolution from an ancestral commensal bacterium, N.

The continued worldwide incidence of gonorrhoeal infection, coupled with the rising resistance to antimicrobials and the difficulties in controlling the disease in developing countries, highlights the need to better understand the molecular basis of N. This knowledge will facilitate disease prevention, surveillance and control, improve diagnostics and may help to facilitate the development of effective vaccines or new therapeutics.

In this Review, we discuss sex-related symptomatic gonorrhoeal disease and provide an overview of the bacterial factors that are important for the different stages of pathogenesis, including transmission, colonization and immune evasion, and we discuss the problem of antibiotic resistance.

The urogenital tract is a complex environment composed of many different types of epithelial tissues and innate immune cells that sample the surrounding milieu.

As a host-adapted organism, Neisseria gonorrhoeae can interact with only human forms of many molecules. Moreover, owing to environmental heterogeneities as well as unknown concentrations of oxygen and nutrients in this niche, substantial challenges exist for developing tissue culture and animal models.

Advances in standardizing the cell culture techniques of primary tissue culture and transgenic mouse models may help to ameliorate these challenges. Although the prevailing view is that infections in women are mainly asymptomatic whereas infections in men are not, many studies show that asymptomatic infections are prevalent in both sexes. The observations underlying the current dogma likely come from physiological and anatomical differences in the male and female urogenital tracts, making neutrophil influx in men much more noticeable and easier to diagnose than infections in women.

The host-restricted pathogen has subsequently evolved a moderately small but effective set of regulatory mechanisms to quickly adapt to changing oxygen and nutrient concentrations. It has yet to be settled in the field whether the vast neutrophil influx following symptomatic infection benefits the host or the pathogen. Owing to its natural competence, propensity for horizontal gene transfer, efficient transformation and dynamic and variable genome, N. With worldwide antimicrobial resistance on the rise, it is necessary to understand the mechanisms by which resistance determinants confer resistance and to develop novel therapies to avoid an era of untreatable gonorrhoea.

The Neisseria genus is composed of many commensals and one other pathogen, Neisseria meningitidis , that are closely related to N. Owing to this similarity, it is often difficult to determine which factors are specific virulence factors for N. More research is needed to determine which factors confer pathogenicity and differentiate between these two pathogens.

World Health Organization. Carmona-Gutierrez, D. Sexually transmitted infections: old foes on the rise. Cell 3 , — Unemo, M. The novel WHO Neisseria gonorrhoeae reference strains for global quality assurance of laboratory investigations: phenotypic, genetic and reference genome characterization. Newman, L. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in based on systematic review and global reporting.

Lee, J. Gonococcal keratoconjunctivitis in adults. Eye 16 , — Noble, R. Pharyngeal colonisation by Neisseria gonorrhoeae and Neisseria meningitidis in black and white patients attending a venereal disease clinic. Danby, C. Patterns of extragenital chlamydia and gonorrhea in women and men who have sex with men reporting a history of receptive anal intercourse.

Little, J. Gonorrhea: update. Oral Surg. Sandstrom, I. Etiology and diagnosis of neonatal conjunctivitis. Acta Paediatr. Masi, A. Clinical manifestations, diagnosis, complications, treatment, and prevention. Arthritis Rheum. Hoffman, O. Pathophysiology and treatment of bacterial meningitis. Marri, P. Genome sequencing reveals widespread virulence gene exchange among human Neisseria species. Liu, G. Non-pathogenic Neisseria: members of an abundant, multi-habitat, diverse genus.

Microbiology , — Maiden, M. Population and functional genomics of Neisseria revealed with gene-by-gene approaches. Bratcher, H. A gene-by-gene population genomics platform: de novo assembly, annotation and genealogical analysis of representative Neisseria meningitidis genomes. BMC Genomics 15 , Joseph, B.

Virulence evolution of the human pathogen Neisseria meningitidis by recombination in the core and accessory genome. Population genomics: diversity and virulence in the Neisseria.

Edwards, J. The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Sparling, P. Biology of Neisseria gonorrhoeae. Walker, C. Gonorrhea infection in women: prevalence, effects, screening, and management. Women' Health 3 , — Jordan, S. Meatal swabs contain less cellular material and are associated with a decrease in Gram stain smear quality compared to urethral swabs in men.

Muzny, C. Sexually transmitted infection risk among women is not fully explained by partner numbers. South Med. Grimley, D.

Sexually transmitted infections among urban shelter clients. Geisler, W. Chlamydial and gonococcal infection in men without polymorphonuclear leukocytes on gram stain: implications for diagnostic approach and management. Xiong, M. Analysis of the sex ratio of reported gonorrhoea incidence in Shenzhen, China.

BMJ Open 6 , e This epidemiological study of 1, male and 1, female participants in Shenzhen, China, shows that undiagnosed, unreported gonorrhoea infections were common in both men and women and that the reported incidence sex ratio was overestimated by a factor of 7. Hook, E. Gender differences in risk for sexually transmitted diseases. Hedges, S. Limited local and systemic antibody responses to Neisseria gonorrhoeae during uncomplicated genital infections.

Fichorova, R. Distinct proinflammatory host responses to Neisseria gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells. Papp, J. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae — MMWR Morb. Wkly Rep. James-Holmquest, A. Differential attachment by piliated and nonpiliated Neisseria gonorrhoeae to human sperm.

Harvey, H. Gonococcal lipooligosaccharide is a ligand for the asialoglycoprotein receptor on human sperm. This study shows that gonococcal LOS binds to asialoglycoprotein receptor 1 ASGPR1 on human sperm, possibly contributing to male-to-female transmission.

Cohen, M. Human experimentation with Neisseria gonorrhoeae : rationale, methods, and implications for the biology of infection and vaccine development.

Next What makes some people resistant to HIV infection? Asked in Microbiology What causes Neisseria gonorrhea? Some specific strains of N. STD Modules. Conditions and Diseases.

Gonorrhea pathogenesis

Gonorrhea pathogenesis

Gonorrhea pathogenesis. Drug Resistance

This site uses Akismet to reduce spam. Learn how your comment data is processed. Culture Media Tests microbes Difference Between. News Ticker. Neisseria gonorrhoeae Gram negative diplococci. About tankeshwar Articles. Hello, thank you for visiting my blog.

I am Tankeshwar Acharya. Blogging is my passion, I am working as an Asst. Previous Virulence factors produced by Neisseria meningitidis and their roles in pathogenesis.

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Gonorrhea: Pathogenesis | Calgary Guide

Etiology, transmission and protection: Neisseria gonorrhoeae the gonococcus is the etiological agent for the strictly human sexually transmitted disease gonorrhea. Infections lead to limited immunity, therefore individuals can become repeatedly infected. Occasionally, the organism can disseminate as a bloodstream infection. Epidemiology, incidence and prevalence: Gonorrhea is a global disease infecting approximately 60 million people annually.

In the United States there are approximately , cases each year, with an incidence of approximately cases per , population. Treatment and curability: Gonorrhea is susceptible to an array of antibiotics.

Currently, third generation extended-spectrum cephalosporins are being prescribed. Molecular mechanisms of infection: Gonococci elaborate numerous strategies to thwart the immune system. The organism expresses IgA protease which cleaves mucosal antibody. The organism can become serum resistant due to its ability to sialylate lipooligosaccharide in conjunction with its ability to subvert complement activation.

The gonococcus can survive within neutrophils as well as in several other lymphocytic cells. The organism manipulates the immune response such that no immune memory is generated which leads to a lack of protective immunity. Neisseria gonorrhoeae the gonococcus is a Gram-negative diplococcus, an obligate human pathogen, and the etiologic agent of the sexually transmitted disease, gonorrhea.

The gonococcus infects a diverse array of mucosal surfaces, some of which include the urethra, the endocervix, the pharynx, conjunctiva and the rectum 1. Worldwide, In most cases, the disease is a noncomplicated mucosal infection. However, in a few patients, generally with women, more serious sequelae can occur and include salpingitis acute inflammation of the fallopian tubes , pelvic inflammatory disease PID; an infection in the upper part of the female reproductive system , or, in rare cases, as a bacteremic infection 4.

If left untreated, these more serious complications can result in sterility, ectopic pregnancy, septic arthritis, and occasionally death. However, the occurrence of PID has significantly decreased over time 6 , 7 , 8 , with an estimated 40, cases of infertility in women annually 9. Dissemination rarely occurs, but when the bacteria do cross the endothelium, they can spread to other locations in the body. Currently, a more worrying trend has emerged, in that, there now appears to be an increased risk for HIV infection in patients that are also infected with N.

Gonorrhea the disease was initially described approximately 3, years ago, but it was not until that Albert Neisser determined the etiologic agent of the disease The Neisseriae are usually regarded as microaerophilic organisms.

However, under the appropriate conditions, they are capable of anaerobic growth In vitro cultivation of this fastidious organism has always been problematic and it was not until the development of an improved Thayer-Martin medium that early epidemiological studies could be undertaken. Subsequently, other commercial growth mediums have since been developed which has allowed for a greater understanding of the disease process.

Like many Gram-negative bacterial pathogens, N. Considerable attention was paid to pili stemming from the observations of Kellogg and coworkers 12 , 13 that virulent T1, T2 organisms and avirulent T3, T4 organisms strains could be differentiated on the basis of colony morphology following growth on solid medium.

Subsequently, it was established that all freshly isolated gonococci possessed thin hair-like appendages pili which were predominantly composed of protein initially called pilin but subsequently renamed PilE Due to their prominent surface location, pili were initially thought to be an ideal vaccine candidate as pilus-specific antibodies were observed in genital secretions However, two prominent vaccine trials failed, with evidence indicating that pilus protein s underwent antigenic variation Gonococcal pili are categorized as Type IV pili, as the PilE polypeptide is initially synthesized with a short 7 amino acid N-terminal leader peptide, which is then endo-proteolytically cleaved The PilE polypeptide consists of three functional domains based on sequence characteristics The N-terminal domain is highly conserved and is strongly hydrophobic, with this region of the protein comprising the core of the pilus structure Assembly of the pilus structure is complicated and involves other proteins besides PilE e.

During pilus biogenesis, and prior to assembly, the leader peptide is removed from PilE by the PilD peptidase The N-terminal domain then facilitates translocation across the cytoplasmic membrane allowing PilE subunits to be polymerized at the inner membrane 29 , As the pilus structure is assembled, it is extruded to the exterior of the outer membrane using the PilQ pore forming complex 29 , 30 , PilC is a minor protein located at the tip of pilus as well as being present at its base.

The pilC gene exists as 2 homologous, but non-identical copies, pilC1 and pilC2 in most gonococcal strains, with only the pilC2 gene being expressed in piliated N. PilC participates in pilus biogenesis as well as in host cell adherence, as pilC mutants prevent the formation of pili by negatively affecting their assembly process, which leads to the bacteria being unable to adhere to human epithelial cells In addition to promoting attachment to host cells, type IV pili are also involved in bacterial twitching motility, biofilm formation, and DNA transformation The binding and uptake of exogenous DNAs by N.

Despite sharing sequence similarity to PilE in the N-terminal domain, ComP was shown to be dispensable to Tfp biogenesis Recently, ComP has been shown to preferentially bind to DUS-containing DNAs via an electropositive stripe on its surface 38 with uptake of the DNA being facilitated by de-polymerization of the pilus structure through PilT hydrolytic activity The coordinated physical retraction and elongation of pili can lead to "twitching", a form of motility that propels the cell along a surface.

The molecular size of Por varies between strains, yet, within individual strains, it exists as only a single protein species Por has been used as the basis for serological classification of gonococci 41 with nine distinct serovars being identified Overall, there are two distinct structural classes PorA and PorB 42 , with the PorA subgroup tending to be associated with the more complicated aspects of the disease, whereas the PorB subgroup is more likely to be involved with uncomplicated mucosal infections Porins allow the transport of ions and nutrients across the outer membrane and can also contribute to the survival of the bacteria in host cells Moreover, gonococcal Por protein has been shown to translocate from the outer membrane into artificial black lipid membranes 45 as well as into epithelial cell membranes, following attachment of the bacteria Por can also transfer into mitochondria of infected cells which leads to the formation of porin channels in the mitochondrial inner membrane, causing increased permeability This causes the release of cytochrome c and other proteins, leading to apoptosis of infected cells However, Por-induced apoptosis remains controversial.

In direct contrast to events with the gonococcus, Neisseria meningitidis Por, which also interacts with mitochondria, apparently protects cells from undergoing apoptosis Interestingly, mitochondrial porins and Neisseria PorB share similar properties, with both protein species being capable of binding nucleotides and exhibiting voltage-dependent gating Por protein also modulates phagosome maturation by changing the phagosomal protein composition through the increase of early endocytic markers and the decrease of late endocytic markers, which ultimately delays phagosome maturation Opa proteins are integral outer membrane proteins and cause colonies to appear opaque due to inter-gonococcal aggregation when viewed by phase-contrast microscopy 52 , 53 , Opa proteins belong to a multigene family with a single gonococcal cell possessing up to 12 opa genes that are constitutively transcribed 55 , Each gene contains conserved, semivariable and 2 hypervariable regions, with the hypervariable segments of the proteins being located on the outside of the outer membrane A single cell is capable of expressing either none to several different Opa proteins 57 , Unlike pili, Opa expression is not required for the initial attachment of gonococci to the host.

However, as an infection proceeds, Opa expression varies 58 , and Opa-expressing bacteria can be observed in epithelial cells and neutrophils upon re-isolation from infected human volunteers 59 , The invasive capacity of N. Individual Opa proteins bind to a variety of receptors on human cells through their exposed hypervariable regions. The binding specificity for human receptors falls into two groups: OpaHS which recognize heparin sulfate proteoglycans 62 , 63 ; and, OpaCEA which recognize the carcinoembryonic antigen cell adhesion molecule CEACAM family that is comprised of the various CD66 molecules 64 , 65 , 66 , CEACAMs are the major receptors of Opa proteins and are expressed on many different cell types including epithelial, neutrophil, lymphocyte and endothelial cells As with all Gram-negative bacteria, gonococci possess lipopolysaccharide in the outer membrane.

Due to its surface exposure, gonococcal LOS is a primary immune target along with the major outer membrane protein Por 69 , 70 , Gonococcal LOS is also toxic to fallopian tube mucosa causing the sloughing off of the ciliatory cells The LOS oligosaccharide composition is highly variable both in length and in carbohydrate content.

Consequently, heterogeneous LOS molecules can be produced by a single cell. However, distinct forms of LOS may be a prerequisite for infection in men The variable oligosaccharide portions of LOS can also mimic host glycosphingolipids, thus promoting bacterial entry In addition, gonococcal LOS can also be sialylated which renders the bacteria resistant to serum killing 77 , 78 , 79 , Consequently, gonococcal LOS contributes to gonococcal pathogenicity by facilitating bacterial translocation across the mucosal barrier as well as by providing resistance against normal human serum 81 , Immunoglobin A IgA protease is another virulence factor in N.

Upon release from the cell, the protein undergoes several endo-proteolytic cleavages, leading to maturation of the IgA protease During an infection, the mature protease specifically targets and cleaves IgA1 within the proline-rich hinge region of the IgA1 heavy chain.

The human IgA2 subclass is not cleaved by gonococcal IgA protease since it lacks a susceptible duplicated octameric amino acid sequence Neisseria IgA protease also cleaves LAMP1 a major lysosome associated membrane protein , which leads to lysosome modification and subsequent bacterial survival Furthermore, iga mutants are defective in transcytosis of bacteria across an epithelial monolayer Neisseria gonorrhoeae primarily colonizes the urogenital tract after sexual contact with an infected individual The gonococcus can exist as both an extracellular and intracellular organism, with the bulk of its genes being devoted to colonization and survival, due to the fact that it cannot survive outside of a human host Transmission is generally a consequence of sexual intercourse.

Upon arrival into a new host, micro-colony formation commences on non-ciliated columnar epithelial cells approximately 1 to 2 hours post-infection 90 , Once bound, the pilus structures on some organisms are retracted through PilE depolymerization 39 which promotes tighter contact with the host cells through Opa binding to the CEACAM receptors Fig.

Upon CEACAM binding, actin polymerization and rearrangement is induced within the host cell which results in bacterial engulfment, transcellular transcytosis and release of the bacteria into the subepithelial layer Fig. The thin, hair-like pilus appendages provide the initial contact with receptors on the surface of the mucosal cells. This figure is based on In vivo , the coordinated expression of pili and Opa varies considerably Organisms isolated from the male urethra generally co-express pili and one of several Opa proteins However, in women, Opa expression varies depending upon the stage of the menstrual cycle and whether or not the patient is taking oral contraceptives At mid-cycle, bacteria isolated from the cervix express Opa, whereas those isolated during menses tend to be Opa negative Moreover, organisms isolated from infected fallopian tubes are almost universally Opa negative, even though Opa expressing organism can be isolated from the cervix of the same patient These observations can perhaps be explained by the fact that cervical secretions during menstruation contain more proteolytic enzymes than during the follicular phase.

Consequently, non-Opa expressing cells may be selected due to the extreme sensitivity of Opa proteins to trypsin-like enzymes. Nonetheless, in the absence of these receptors, gonococci were found to still adhere and invade. Consequently, CECAM expression, or the lack of it, possibly allows for in vivo phenotypic selection of distinct gonococcal populations on various tissues

Gonorrhea pathogenesis

Gonorrhea pathogenesis