Full Answer
What is the virulence factor of Neisseria gonorrhoeae?
As N. gonorrhoeae progresses through the stages of disease pathogenesis: transmission, adherence, colonization and invasion, and immune evasion, the bacterium expresses many virulence factors to promote survival and replication while remaining minimally invasive and discoverable by immune cells. It has yet to be settled in the filed whether the vast neutrophil …
What is the treatment for gonorrhea?
Sep 05, 2016 · 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.
What is the pathophysiology of gonorrhea?
Gonorrhea has become resistant to most conventional antimicrobials used in clinical practice. The global spread of multidrug-resistant isolates of Neisseria gonorrhoeae could lead to an era of untreatable gonorrhea. ... Gonococcal lipooligosaccharide sialylation: virulence factor and target for novel immunotherapeutics Pathog Dis. 2017 Jun 1;75 ...
Is disabling key gonococcal virulence mechanisms effective?
Disabling key gonococcal virulence mechanisms is an effective therapeutic strategy because the reduction of virulence is likely to be accompanied by a loss of fitness, rapid elimination by host immunity and consequently, decreased transmission. gonorrhea, lipooligosaccharide, sialic acid, complement, factor H, immunotherapeutic ABBREVIATIONS
What is the virulence factor of gonorrhea?
Like many Gram-negative bacterial pathogens, N. gonorrhoeae possesses a wide range of virulence determinants, which include the elaboration of pili, Opa protein expression, lipooligosaccharide expression (LOS), Por protein expression and IgA1 protease production that facilitates adaptation within the host.Sep 5, 2016
How does gonorrhea evade the immune system?
gonorrhoeae can evade host immune defenses by multifactorial strategies including continuous changes in its surface antigenic structure, resistance to complement-mediated bacteriolysis, and possibly the production of IgA1 protease.Jun 12, 2013
How does Neisseria gonorrhoeae deal with the toxic effect of oxygen?
N. gonorrhoeae cells exposed to serum- or phagocyte-derived lactate have increased metabolism, including increased lactate dehydrogenase activity, and rapidly consume available molecular oxygen, reducing the ability of PMNs to mount an oxidative response (29-31, 82).
Which are the main virulence factors of N. gonorrhoeae quizlet?
The main virulence factor of N. gonorrhoeae is the pili (fimbriae), which allows attachment to mucosal surface and prevention of phagocytosis.
What are the virulence factors of Chlamydia trachomatis?
A number of candidate virulence factors have been identified, including the polymorphic outer membrane autotransporter family of proteins, the putative large cytotoxin, type three secretion effectors, stress response proteins and proteins or other regulatory factors produced by the cryptic plasmid.
What are the main cell surface structures on N. gonorrhoeae needed for adhesion invasion and immune evasion in pathogenesis?
a) N. gonorrhoeae uses an array of surface structures to adhere to host cells, occasionally invade host cells, and evade the immune system18,142,143. These surface structures include Type IV pili, LOS, porin, and Opa proteins.Jan 11, 2019
Why is Neisseria gonorrhoeae resistant to antibiotics?
The ceftriaxone-resistance mutations alter the bacterial enzyme that is the target of ceftriaxone, making it harder for the drug to bind to the enzyme but at the same time making it less able for the enzyme to build and repair bacterial cell walls.Apr 4, 2018
What is the virulence factor of Neisseria meningitidis?
The virulence (14) of N. meningitidis is influenced by multiple factors: capsule polysaccharide expression, expression of surface adhesive proteins (outer membrane proteins including pili, porins PorA and B, adhesion molecules Opa and Opc), iron sequestration mechanisms, and endotoxin (lipooligosaccharide, LOS).
What is the morphology of Neisseria gonorrhoeae?
Morphology of Neisseria gonorrhoeae: Under the microscope, it appears as a gram-negative coccus which is present in pairs (diplococci) with the flattening of the adjacent sides. The diameter ranges from 0.6-1 μm. The diplococci have kidney/coffee bean shape.Nov 20, 2020
What test can be used to quickly differentiate between Neisseria meningitidis and Neisseria gonorrhoeae quizlet?
Sugar fermentation is used to distinguish Neisseria meningitidis from Neisseria gonorrhoeae.
What is the name of the organism which causes epidemic of meningitis in college dorms quizlet?
Meningococcal meningitis is caused by a bacterium known as Neisseria meningitidis. There are several types, or serogroups, of Neisseria meningitidis.
Why is agar an important component of media?
Agar is an ideal solidifying agent for microbiological media because of its melting properties and because it has no nutritive value for the vast majority of bacteria. Solid agar melts at about100°C; liquid agar solidifies at about 42°C.
What is the function of PorB?
Major outer membrane porin (PorB) expressed by Neisseria gonorrhoeae plays multiple roles during infection, in addition to its function as an outer membrane pore. PorB is a voltage-gated pore that mediates ion exchange between N. gonorrhoeae and the environment.
What is the role of a pili?
Fimbriae/Pili. Pili is the principal virulence factor of gonococci. It plays a major role in adherence and also prevents bacteria from phagocytosis. It helps in the attachment of the Neisseria gonorrhoeae to microvilli of nonciliated columnar epithelial cells. Pili are composed of pilin proteins which are antigenically distinct, ...
What is the gram negative diplococcus?
Last updated on May 20th, 2021. Neisseria gonorrhoeae, the gonococcus, is a gram-negative diplococcus that causes the sexually transmitted disease, gonorrhea. Gonorrhea commonly manifests as cervicitis, urethritis, and conjunctivitis.
What is the role of opa in epithelial cells?
They are a family of antigenically distinct outer membrane proteins that undergo phase-variable expression. Opa proteins promote persistence of N. gonorrhoeae in the female genital tract and opa gene phase variation allows gonococci to invade human epithelial cells.
What are outer membrane proteins?
Outer membrane proteins (PorB) 1 induce or inhibit apoptotic signaling, 2 contribute to serum resistance via interactions with regulators of the classical and alternative complement pathway, 3 mediate epithelial cell invasion under low-phosphate conditions, 4 can affect the generation of reactive oxygen species (ROS) by innate immune cells.
What are the three pathways of complement activation?
Complement activation on microbial surfaces occurs through three pathways, namely the classical, lectin and alternative (Fig. 1 ). The classical pathway is triggered by the binding of antibodies (IgM and IgG (mainly the IgG3 and IgG1 subclasses in humans)) to an antigen, which engages the C1 complex that then activates C4, which leads to C4b deposition. The lectin pathway leads to C4b deposition on surfaces following binding of complexes of mannan binding lectin (MBL), ficolins or collectins and the MBL-associated serine proteases (MASPs). The alternative pathway is characterized by a positive feedback loop, where C3b deposited on the bacterial surface is amplified by factors B and D that lead to the formation of C3 convertases. All three complement pathways converge at the level of C3 deposition. Downstream activation of complement results in the formation of C5 convertases, which lead to generation of the C5b-9 complex, also called the membrane attack complex that can insert into the membrane of Gram-negative bacteria and kill the organism. In physiological conditions, the complement cascade is kept under control by inhibitors such as C4b-binding protein (C4BP), factor H (FH) and vitronectin. A detailed description of the complement pathways and its inhibition, while beyond the scope of this review, can be found elsewhere (Walport 2001; Ricklin et al. 2010 ). LOS sialic acid inhibits all three pathways of complement as described below.
Can neutrophils kill gonococci?
Gonococci may be taken up and killed by neutrophils either through opsonic (i.e. antibody and complement dependent) or non-opsonic (independent of Fc and complement receptors) means (Rest et al. 1982 ). Sialylation of LOS decreases opsonic killing of gonococci (Kim et al. 1992; Rest and Frangipane 1992; Gill et al. 1996 ), which may be in part because of decreased complement activation and C3 fragment deposition on the surface of sialylated bacteria (Jarvis 1994; Ram et al. 1998 ). Lactate present in PMNs may further facilitate LOS sialylation (Parsons et al. 1996a, b) and promote bacterial survival.
Is gonorrhea a public health problem?
Gonorrhea is a major international public health problem. About 78 million new cases of gonococcal infection are estimated to occur worldwide, annually (Newman et al. 2015 ); almost 400 000 of these are reported in the USA. Gonorrhea can result in serious sequelae in women, including infertility, ectopic pregnancy and chronic pelvic pain. Furthermore, concomitant infection with HIV and gonorrhea can enhance the rate of transmission of HIV 5-fold (Laga et al. 1993 ). Neisseria gonorrhoeae has developed resistance to every antimicrobial it has encountered (Unemo and Shafer 2011 ). The emergence of multidrug-resistant isolates in Asia, Europe and Australia (Ohnishi et al. 2011; Camara et al. 2012; Lahra, Ryder and Whiley 2014) has led to N. gonorrhoeae being called a ‘superbug’ (Unemo and Nicholas 2012) and has ushered in an era of potentially untreatable gonococcal infection (Bolan, Sparling and Wasserheit 2012 ). The US Centers for Disease Control and Prevention (CDC), for the first time, has prioritized drug-resistant N. gonorrhoeae as ‘urgent’ (one of three bacterial organisms) in a list of microbes that are otherwise considered serious (12) or concerning (3) (CDC 2013 ). The importance of addressing this problem using novel approaches cannot be overemphasized. Interfering with bacterial virulence mechanisms offers an attractive option for therapeutics. In this review, we discuss the importance of a 9-carbon sugar called sialic acid in gonococcal virulence and how gonococcal sialic acid can be targeted by two novel immunotherapeutics.
Does MBL bind to glycans?
MBL prefer entially recognizes glycans that terminate in mannose, glucose, fucose or N -acetylglucosamine (GlcNAc) (Weis, Drickamer and Hendrickson 1992 ). MBL binds to several strains of N. gonorrhoeae in varying amounts (Gulati et al. 2002 ). Binding of MBL to N. gonorrhoeae strains MS11 (Devyatyarova-Johnson et al. 2000) and 24-1 (Gulati et al. 2002) decreases following LOS sialylation. Surface-bound MBL-MASP complexes activate complement on N. gonorrhoeae only when purified MBL-MASP is incubated with bacteria prior to the addition of serum. However, the MBL pathway does not appear to contribute to C4b deposition in the context of ‘whole’ serum or when MBL-deficient serum is first reconstituted with purified MBL-MASP and then added to bacteria (Gulati et al. 2002 ). This MASP function is blocked by C1 inhibitor and α 2 -macroglobulin in serum (Gulati et al. 2002 ). Although not understood, a possible explanation for why these inhibitors do not block complement activation when purified MBL-MASP is pre-incubated with bacteria is that they cannot associate with MASP once the MBL-MASP complex has associated with gonococci. Overall, the role of the lectin pathway in host defenses against N. gonorrhoeae remains controversial.
Is gonorrhea resistant to antimicrobials?
Gonorrhea has become resistant to most conventional antimicrobials used in clinical practice. The global spread of multidrug-resistant isolates of Neisseria gonorrhoeae could lead to an era of untreatable gonorrhea. New therapeutic modalities with novel mechanisms of action that do not lend themselves to the development of resistance are urgently needed. Gonococcal lipooligosaccharide (LOS) sialylation is critical for complement resistance and for establishing infection in humans and experimental mouse models. Here we describe two immunotherapeutic approaches that target LOS sialic acid: (i) a fusion protein that comprises the region in the complement inhibitor factor H (FH) that binds to sialylated gonococci and IgG Fc (FH/Fc fusion protein) and (ii) analogs of sialic acid that are incorporated into LOS but fail to protect the bacterium against killing. Both molecules showed efficacy in the mouse vaginal colonization model of gonorrhea and may represent promising immunotherapeutic approaches to target multidrug-resistant isolates. Disabling key gonococcal virulence mechanisms is an effective therapeutic strategy because the reduction of virulence is likely to be accompanied by a loss of fitness, rapid elimination by host immunity and consequently, decreased transmission.
What are the strains of N. gonorrhoeae?
gonorrhoeae have been associated with asymptomatic infections of urogenital sites; these include strains that require arginine, hypoxanthine, and uracil (AHU) or proline, arginine (citrulline), and uracil (PAU) to grow on chemically defined media on which gonococcal strains are characterized.
What serogroups are associated with meningitis?
Certain types of N. meningitidis are usually associated with meningitis. Of a total of 13 serogroups of N. meningitidis, strains belonging to the serogroups A, B, C, and W-135 have most frequently been associated with epidemics.
Is Moraxella catarrhalis a pathogen?
For decades, M. catarrhalis was thought to be normal flora of the oro- and nasopharynx. M. catarrhalis is now recognized to be a pathogen which causes pneumonia, systemic disease, sinusitis, otitis media and ophthalmia neonatorum.
Is Neisseria gonorrhoeae pathogenic?
Of the Neisseria and related species, only N. gonorrhoeae is considered always to be pathogenic i. e., cause disease . N. gonorrhoeae is not considered to be normal flora under any circumstances.
Fimbriae/Pili
OuterMembrane Proteins
- Majorouter membrane porin (PorB) expressed by Neisseriagonorrhoeaeplaysmultiple roles during infection, in addition to its function as anouter membrane pore. PorBis a voltage-gated pore that mediates ion exchange between N.gonorrhoeae andthe environment. PorB also appears to perform multiple functionscontributing to N.gonorrhoeaepathogenesis; 1. induce or inhibit apopt…
Neisserial Opacity (OPA) Proteins
- They are a family of antigenically distinct outer membrane proteins that undergo phase-variable expression. Opa proteins promote persistence of N. gonorrhoeae in the female genital tract and opagene phase variation allows gonococci to invade human epithelial cells. Transferrinbinding proteins Neisseria gonorrhoeaeproduces two transferrin binding pr...
IGA Proteases
- Strains of N. gonorrhoeae produce two distinct extracellular IgA1 proteases that cleave the heavy chain of the human immunoglobulin IgAat different points within the hinge region. Split products of IgA1 have been found in the genital secretions of women with gonorrhea. Lipooligosaccharide: Lipooligosaccharide (LOS) of Neisseria gonorrhoeae activates the alternative complement path…