Members of the genus Neisseria include pathogens causing important human diseases such as meningitis, septicaemia, gonorrhoea and pelvic inflammatory disease syndrome. Neisseriae are found on the exposed epithelia of the upper respiratory tract and the urogenital tract. Colonisation of these exposed epithelia is dependent on a Hocke von Prostatitis of diverse bacterial molecules, extending not only from the surface of the bacteria but also found within the outer membrane.
During invasive disease, pathogenic Neisseriae also interact with immune effector cells, vascular endothelia and the meninges. Neisseria adhesion involves the interplay of these multiple surface factors and in this review we discuss the structure and function of these important molecules and the nature of the host cell receptors and mechanisms Hocke von Prostatitis in their recognition.
We also describe the current status for recently identified Neisseria adhesins. Understanding the biology of Neisseria adhesins has an impact not only on the development of Hocke von Prostatitis vaccines but also in revealing fundamental knowledge about human biology.
This organism was later reclassified as a member of the genus Neisseriaafter the German physician Albert Neisser — who discovered in the diplococcus known as Neisseria gonorrhoeae. Inthe Hocke von Prostatitis physicians and zoologists Ettore Marchiafava — and Angelo Celli — described the presence of oval micrococci within leucocytes in the CSF of patients dying Hocke von Prostatitis meningitis [ 2 Hocke von Prostatitis, and inthe German physicians and microbiologists Johann Heubner — and F.
Kiefer were the first to isolate meningococci from the CSF and throat of living patients [ 345 ]. Neisseria meningitidis the meningococcus causes approximatelycases of infection per year globally and up to 50, deaths [ 17 ].
The incidence of meningococcal disease ranges from less than 0. The distinguishing features of Hocke von Prostatitis disease are the fulminant clinical course and the ability Hocke von Prostatitis cause large-scale epidemics.
The French physician Gaspard Vieusseux — is generally credited with the first detailed description of epidemic meningitis in in the environs of Geneva, with 33 deaths occurring during a three-month period.
His cases show classical Hocke von Prostatitis signs of meningococcal meningitis in children, with rapid onset and death within 24—48 h [ 19 ].
Moreover, children presenting without meningeal irritation showed signs of fulminant disease, including violent abdominal Hocke von Prostatitis, vomiting, diarrhoea and Hocke von Prostatitis presence of livid spots on the skin.
The clinical manifestations of meningococcal disease can be classified into 1 bacteraemia without sepsis; 2 meningococcaemia without meningitis; 3 meningitis with or without meningococcaemia and 4 meningoencephalitis [ 2021 ]. These clinical presentations are not mutually exclusive and often overlap in individual patients and they are more useful as prognostic predictors [ 20 ].
Brandtzaeg et al. This classification has been used in clinical studies of meningococcal disease occurring amongst subjects and a higher mortality rate was observed in patients with shock [ 22 ]. The most common presentation of invasive meningococcal disease is meningitis, while fulminant meningococcal septicaemia has a higher mortality Hocke von Prostatitis [ 23 ].
Critical cases may develop disseminated intravascular coagulation DIC and acute adrenal haemorrhage. In cases with severe meningococcaemia, intravascular thrombosis and haemorrhagic necrosis can cause dramatic widespread purpura fulminans with potential infarction and gangrene of limbs [ Hocke von Prostatitis23 ].
Other syndromes associated with meningococcal disease include acute respiratory distress syndrome ARDS Hocke von Prostatitis, conjunctivitis, otitis media, epiglottitis, urethritis, arthritis, pericarditis, conus medullaris syndrome and cranial nerve dysfunction, especially of the 6th, 7th and Hocke von Prostatitis cranial nerves. Severe pericarditis, which is likely to result from an immunological reaction thought to be endotoxin-related, can complicate massive tamponade [ 212425 ].
Early administration of antibiotics is the key factor leading to full recovery. Empirically, a third-generation cephalosporin e. Penicillin G is still the drug Hocke von Prostatitis choice if the antibiotic susceptibility of the causative meningococcus is known.
Alternatively, chloramphenicol can also be effective [ 26 ]. However, survivors who do not display gross neurological damage can often show more subtle neurodevelopmental sequelae, e. Neisseria gonorrhoeae the gonococcus is the causative agent of gonorrhoea, which has affected humans for thousands of years and is still a commonly reported sexually transmitted disease STD worldwide.
Every year, this exclusively human pathogen afflicts an estimated 62 million people [ 30 ]. Gonococcal infection can often be asymptomatic and depending on Hocke von Prostatitis anatomical site of exposure, clinical infection can be urogenital, anorectal or pharyngeal gonorrhoea.
The major symptoms of urogenital infection in men include urethral discharge and dysuria and the most common localized complication is acute epididymitis: other complications include penile lymphangitis, periurethral abscess, acute prostatitis, and seminal vesiculitis. By contrast, the natural course of gonococcal infection is less well understood in women and there are probably more cases of subclinical infection in women than men.
The primary site of female genital infection is the mucosal columnar epithelium in the endocervix, whilst the squamous epithelium of the vaginal mucosa is influenced by oestrogen and not susceptible to gonococcal infection. In women, gonococcal infection can cause cervicitis, endometritis or salpingitis inflammation in the fallopian tube.
Complicated ascending gonococcal infection can lead to pelvic inflammatory disease PIDectopic pregnancy and infertility in women [ 31 ]. In addition, Hocke von Prostatitis with gonococci and Chlamydia trachomatis is common [ 3233 ] and moreover, gonococcal infection can facilitate transmission of human immunodeficiency virus HIV [ 34 ]. Other local manifestations include gonococcal conjunctivitis, gingivitis, intraoral and cutaneous abscess formation.
Pharyngeal gonococcal infections are mostly asymptomatic and resolve spontaneously. Infants born to infected Hocke von Prostatitis are at high risk of acquiring gonococcal conjunctivitis ophthalmia neonatorumwhich can cause childhood blindness.
This arthritis is often asymmetric and involves a Hocke von Prostatitis joints, in contrast to polyarthritis, which is caused by immune complex-mediated disorders. Characteristic dermatitis may present as papules and pustules, often with a haemorrhagic component.
Although uncommon, direct extension of N. Effective treatment is essential for disease control. However, the increase in antibiotic-resistant gonococcal strains worldwide is worrying and fromthe Centerfor Disease Control CDC no longer recommends oral cephalosporins for treating gonococcal infections [ 35 ].
A combination therapy consisting of a single intramuscular injection dose of ceftriaxone mg and oral azithromycin 1 gis essential to slow down the development of drug resistance [ Hocke von Prostatitis ]. Members of the genus Neisseria colonise exposed mucosal epithelial surfaces of mammalian species, but as demonstrated Hocke von Prostatitis in Hocke von Prostatitis pathology of Neisseria infections, the ability to disseminate Hocke von Prostatitis sites of colonisation also provides the opportunity for bacterial interactions with a wide variety of host cell types and organ systems.
In this review, we examine the process of adhesion of Neisseria species to target mammalian host cells and tissues, by focusing on the i biology and structure of adhesins; and ii the mechanisms involved in their interactions. We examine also Neisseria surface structures that are involved in adhesion but not defined strictly as adhesins. To colonize host cells successfully, Neisseria spp. The first Hocke von Prostatitis between the bacterium and host cells Hocke von Prostatitis the process of adhesion, which can depend on the interaction of specific bacterial surface molecules—adhesins—with specific host cell receptors.
Colonization or maintenance of association with host cells involves adhesion, bacterial aggregation, microcolony and biofilm formation and the avoidance of host immunity. To begin, we focus on the biology and structure of Neisseria adhesins.
Commonly found in Gram-negative bacteria [ Hocke von Prostatitis ], the Tfp imparts twitching motility by rapid extension and retraction [ 38 ] and facilitates uptake of foreign DNA to increase transformation frequency [ 39 ].
Meningococci are capable of producing two structurally distinct types of pili—Class I and II—whilst gonococci only produce Class I pili. The discriminating murine monoclonal antibody SM1 [ 40 ] binds to both meningococcal and gonococcal Class I pili, but not to meningococcal Class II pili [ 41Hocke von Prostatitis ].
Little is known about the expression of Neisserial pili in commensal strains: some strains of N. Moreover, N. Recently, the fimbriae of N. Antigenic variation of Tfp expression, which results from both inter- and Hocke von Prostatitis non-reciprocal DNA recombination between pilS silent genes and pilE genes [ 4147484950 ] is known to contribute to evasion mechanisms employed by pathogenic Neisseria [ 51 ].
Furthermore, pili from different infection sites of the same patient with meningococcal disease can be antigenically diverse [ 52 ]. The frequency of antigenic variation was reported to be 0. Hocke von Prostatitis pili are hair-like, flexible and helically homopolymeric fibres, 6 nm in diameter and several microns in length. PilE the product of the pilE gene Hocke von Prostatitis the pilin subunit that assembles into the multifunctional pilus adhesin and virulence factor [ 55 Hocke von Prostatitis.
To our knowledge, the first report of the preparation of three-dimensional needle- and plate-shaped crystals of purified Hocke von Prostatitis. The best crystals were diffracted to 2.
In a follow-up paper, Parge and colleagues derived the structure of the fibre-forming pilin protein at 2. The crystallographic structure of N. Further X-ray crystallographic refinement of gonococcal pilin to 2.
Dephosphorylation altered the morphology of fibres, but did not affect bacterial adhesion, transformation, piliation or twitching motility. Parge et al. At the same time, cryo-electron microscopy cryo-EM and reconstruction provided a structure for gonococcal Tfp, in which spiralling three-helix bundles form the filament core, anchor the globular heads and provide strength and flexibility.
Furthermore, PilC has been demonstrated to mediate fibre retraction [ 64 ]. The pilG gene is highly conserved in pathogenic Neisseriae [ 65 ] and the PilG protein plays a role in pilus Hocke von Prostatitis. However, PilG does not appear to be essential for pilus assembly, because apparently normal pili are observed in pilG mutant meningococci [ 61 ]. The conserved Hocke von Prostatitis PilQ is a secretin that forms a pore through which Tfp emerge on the bacterial surface [ 66 ] and PilW is important for Hocke von Prostatitis stability and function of the pilus fibre [ 67 ].
Though low in abundance, PilX plays a role in mediating bacterial aggregation, which is important for bacterial adhesion [ 68 ]. The first three-dimensional structure of the secretin PilQ was resolved at 2. The quaternary structure of the PilQ secretin from N. PilQ is organized as a ring of 12 identical subunits as shown by the presence of a fold rotational symmetry, following self-rotation and power spectrum analysis.
The cavity accommodates neatly the X-ray crystal structure of the N. The structure of the N. More recently, the studies of Jain et al. In this study, secretin complexes of N. In contrast, the spikes were absent and the peripheral ring was partly or completely lacking in N.
When present, the ring has a fold symmetry. Using NMR, Berry et al. The entire PilQ assembly that spans the periplasm has been reconstructed and NMR chemical shift mapping was used to generate a model for the PilP:PilQ interacting complex, adding further information to the three-dimensional reconstruction of the complex obtained previously at low resolution by TEM [ 75 ].
The structures of several other pilus-associated proteins have been resolved. These include solution structures of folded domains of the PilP lipoprotein [ 76 ], the high-resolution crystal structure of PilW, the partner lipoprotein of PilQ from N. The ultrastructure of the N. The most abundant protein adhesins in the outer membrane OM are Opa and Opc. A single meningococcal strain can harbour 3—4 opa genes opaAopaBopaD and opaJ [ 8283 ], whilst up to 11 opa genes can be expressed in gonococci at separate loci throughout the genome [ 84 ].
The commensal strains N. Circular dichroism has been used to determine the structure of refolded and purified opacity proteins OpaJ and OpaB derived from N. Although the crystal structure of Opa remains unsolved, Opa is structurally similar to the Neisserial surface protein Hocke von Prostatitis NspAfor which a crystal structure was reported in [ 90 ].
Little is known about the role of Hocke von Prostatitis as an adhesin.