Neisseria gonorrhoeae

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Neisseria gonorrhoeae
Gonococcal urethritis PHIL 4085 lores.jpg
Gram-stain of gonococcal urethritis. Note distribution in neutrophils and presence of both intracellular and extracellular bacteria. (CDC)
Scientific classification Red Pencil Icon.png
Domain: Bacteria
Phylum: Proteobacteria
Class: Betaproteobacteria
Order: Neisseriales
Family: Neisseriaceae
Genus: Neisseria
Species:
N. gonorrhoeae
Binomial name
Neisseria gonorrhoeae
(Zopf 1885) Trevisan 1885 [1]
Synonyms

Neisseria gonorrhoeae, also known as gonococcus (singular), or gonococci (plural) is a species of Gram-negative diplococci bacteria isolated by Albert Neisser in 1879. [3] It causes the sexually transmitted genitourinary infection gonorrhea [4] as well as other forms of gonococcal disease including disseminated gonococcemia, septic arthritis, and gonococcal ophthalmia neonatorum.

Bacteria A domain of prokaryotes – single celled organisms without a nucleus

Bacteria are a type of biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods and spirals. Bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, and the deep portions of Earth's crust. Bacteria also live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, and only about half of the bacterial phyla have species that can be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology.

Albert Ludwig Sigesmund Neisser was a German physician who discovered the causative agent (pathogen) of gonorrhea, a strain of bacteria that was named in his honour.

Sexually transmitted infection Infection transmitted through human sexual behavior

Sexually transmitted infections (STI), also referred to as sexually transmitted diseases (STD), are infections that are commonly spread by sexual activity, especially vaginal intercourse, anal sex and oral sex. Many times STIs initially do not cause symptoms. This results in a greater risk of passing the disease on to others. Symptoms and signs of disease may include vaginal discharge, penile discharge, ulcers on or around the genitals, and pelvic pain. STIs can be transmitted to an infant before or during childbirth and may result in poor outcomes for the baby. Some STIs may cause problems with the ability to get pregnant.

Contents

It is oxidase positive and aerobic, and it survives within neutrophils. [4] Culturing it requires carbon dioxide supplementation and enriched agar (chocolate agar) with various antimicrobials (Thayer-Martin). It exhibits antigenic variation through recombination of its pili and surface proteins that interact with the immune system. [3]

Chocolate agar Growth medium

Chocolate agar (CHOC) or chocolate blood agar (CBA), is a nonselective, enriched growth medium used for isolation of pathogenic bacteria. It is a variant of the blood agar plate, containing red blood cells that have been lysed by slowly heating to 80°C. Chocolate agar is used for growing fastidious respiratory bacteria, such as Haemophilus influenzae and Neisseria meningitidis. In addition, some of these bacteria, most notably H. influenzae, need growth factors such as nicotinamide adenine dinucleotide and hemin, which are inside red blood cells; thus, a prerequisite to growth for these bacteria is the presence of red blood cell lysates. The heat also inactivates enzymes which could otherwise degrade NAD. The agar is named for its color and contains no chocolate products.

Thayer-Martin agar culture medium used in microbiology

Thayer-Martin agar is a Mueller-Hinton agar with 5% chocolate sheep blood and antibiotics. It is used for culturing and primarily isolating pathogenic Neisseria bacteria, including Neisseria gonorrhoeae and Neisseria meningitidis, as the medium inhibits the growth of most other microorganisms. When growing Neisseria meningitidis, one usually starts with a normally sterile body fluid, so a plain chocolate agar is used. Thayer-Martin agar was initially developed in 1964, with an improved formulation published in 1966.

Antigenic variation refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters its surface proteins in order to avoid a host immune response. It is related to phase variation. Immune evasion is particularly important for organisms that target long-lived hosts, repeatedly infect a single host and are easily transmittable. Antigenic variation not only enables immune evasion by the pathogen, but also allows the microbes to cause re-infection, as their antigens are no longer recognized by the host's immune system. When an organism is exposed to a particular antigen an immune response is stimulated and antibodies are generated to target that specific antigen. The immune system will then "remember" that particular antigen, and defenses aimed at that antigen become part of the immune system’s acquired immune response. If the same pathogen tries to re-infect the same host the antibodies will act rapidly to target the pathogen for destruction. However, if the pathogen can alter its surface antigens, it can evade the host's acquired immune system. This will allow the pathogen to re-infect the host while the immune system generates new antibodies to target the newly identified antigen. Antigenic variation can occur by altering a variety of surface molecules including proteins and carbohydrates. There are many molecular mechanisms behind antigenic variation, including gene conversion, site-specific DNA inversions, hypermutation, as well as recombination of sequence cassettes. In all cases, antigenic variation and phase variation result in a heterogenic phenotype of a clonal population. Individual cells either express the phase-variable protein(s) or express one of multiple antigenic forms of the protein. This form of regulation has been identified mainly, but not exclusively, for a wide variety of surface structures in pathogens and is implicated as a virulence strategy.

Sexual transmission is possible through vaginal, anal, or oral sex. [5] Sexual transmission may be prevented through the use of barrier protection. [6] Perinatal transmission may occur during childbirth, and may be prevented by antibiotic treatment of the mother before birth and the application of antibiotic eye gel on the eyes of the newborn. [6] After an episode of gonococcal infection, infected persons do not develop immunity to future infections. Reinfection is possible due to N. gonorrhoeae's ability to evade the immune system by varying its surface proteins. [7]

N. gonorrhoeae can cause infection of the genitals, throat, and eyes. [8] Asymptomatic infection is common in males and females. [6] [9] Untreated infection may spread to the rest of the body (disseminated gonorrhea infection), especially the joints (septic arthritis). Untreated infection in women may cause pelvic inflammatory disease and possible infertility due to the resulting scarring. [8] Diagnosis is through culture, Gram stain, or polymerase chain reaction testing of a urine sample, urethral swab, or cervical swab. [10] [11] Chlamydia co-testing and testing for other STI's is recommended due to high rates of coinfection. [12]

Pelvic inflammatory disease infection of uterus, fallopian tubes, ovaries or the inner surface of pelvis

Pelvic inflammatory disease, also known as pelvic inflammatory disorder (PID), is an infection of the upper part of the female reproductive system, namely the uterus, fallopian tubes, and ovaries, and inside of the pelvis. Often, there may be no symptoms. Signs and symptoms, when present, may include lower abdominal pain, vaginal discharge, fever, burning with urination, pain with sex, bleeding after sex, or irregular menstruation. Untreated PID can result in long-term complications including infertility, ectopic pregnancy, chronic pelvic pain, and cancer.

Microbiological culture multiplying microorganisms by letting them reproduce in culture media

A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture medium under controlled laboratory conditions. Microbial cultures are foundational and basic diagnostic methods used extensively as a research tool in molecular biology.

Gram stain Method of staining used to differentiate bacterial species into two large groups (gram-positive and gram-negative)

Gram stain or Gram staining, also called Gram's method, is a method of staining used to distinguish and classify bacterial species into two large groups. The name comes from the Danish bacteriologist Hans Christian Gram, who developed the technique.

Microbiology

Neisseria species are fastidious, Gram-negative cocci that require nutrient supplementation to grow in laboratory cultures. Neisseria spp. are facultatively intracellular and typically appear in pairs (diplococci), resembling the shape of coffee beans. Nesseria is non-spore-forming, capable of moving using twitching motility, and an obligate aerobe (requires oxygen to grow). Of the 11 species of Neisseria that colonize humans, only two are pathogens. N. gonorrhoeae is the causative agent of gonorrhea and N. meningitidis is one cause of bacterial meningitis.

<i>Neisseria</i> genus of bacteria

Neisseria is a large genus of bacteria that colonize the mucosal surfaces of many animals. Of the 11 species that colonize humans, only two are pathogens, N. meningitidis and N. gonorrhoeae. Most gonoccocal infections are asymptomatic and self-resolving, and epidemic strains of the meningococcus may be carried in >95% of a population where systemic disease occurs at <1% prevalence.

Twitching motility is a form of crawling bacterial motility used to move over surfaces. Twitching is mediated by the activity of hair-like filaments called type IV pili which extend from the cell's exterior, bind to surrounding solid substrates and retract, pulling the cell forwards in a manner similar to the action of a grappling hook. The name twitching motility is derived from the characteristic jerky and irregular motions of individual cells when viewed under the microscope. It has been observed in many bacterial species, but is most well studied in Pseudomonas aeruginosa, Neisseria gonorrhoeae and Myxococcus xanthus. Active movement mediated by the twitching system has been shown to be an important component of the pathogenic mechanisms of several species.

Obligate aerobe

An obligate aerobe is an organism that requires oxygen to grow. Through cellular respiration, these organisms use oxygen to metabolise substances, like sugars or fats, to obtain energy. In this type of respiration, oxygen serves as the terminal electron acceptor for the electron transport chain. Aerobic respiration has the advantage of yielding more energy than fermentation or anaerobic respiration, but obligate aerobes are subject to high levels of oxidative stress.

Culture and identification

Thayer-Martin agar is selective for growth of Neisseria species. Further testing (oxidase, Gram stain, carbohydrate use) is needed to differentiate N. gonorrhoeae from N. meningitidis Neisseria gonorrhoeae 01.png
Thayer-Martin agar is selective for growth of Neisseria species. Further testing (oxidase, Gram stain, carbohydrate use) is needed to differentiate N. gonorrhoeae from N. meningitidis
Carbohydrate utilization of Neisseria gonorrhoeae: N. gonorrhoeae will oxidise glucose, not maltose, sucrose, or lactose; N. meningitidis ferments glucose and maltose. Carbohydrate fermentation gonorrhea.png
Carbohydrate utilization of Neisseria gonorrhoeae: N. gonorrhoeae will oxidise glucose, not maltose, sucrose, or lactose; N. meningitidis ferments glucose and maltose.

N. gonorrhoeae is usually isolated on Thayer-Martin agar (or VPN) agar in an environment enriched with 3-7% carbon dioxide. [10] Thayer-Martin agar is a chocolate agar plate (heated blood agar) containing nutrients and antimicrobials (vancomycin, colistin, nystatin, and trimethoprim). This agar preparation facilitates the growth of Neisseria species while inhibiting the growth of contaminating bacteria and fungi. Martin Lewis and New York City agar are other types of selective chocolate agar commonly used for Neisseria growth. [10] N. gonorrhoeae is oxidase positive (possessing cytochrome c oxidase) and catalase positive (able to convert hydrogen peroxide to oxygen). [10] When incubated with the carbohydrates lactose, maltose, sucrose, and glucose, N. gonorrhoeae will oxidize only the glucose. [10]

Agar plate

An agar plate is a Petri dish that contains agar as a solid growth medium plus nutrients, used to culture microorganisms. Sometimes selective compounds are added to influence growth, such as antibiotics.

Antibiotic drug used in the treatment and prevention of bacterial infections

An antibiotic is a type of antimicrobial substance active against bacteria and is the most important type of antibacterial agent for fighting bacterial infections. Antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics.

Vancomycin pharmaceutical drug

Vancomycin is an antibiotic used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant Staphylococcus aureus. Blood levels may be measured to determine the correct dose. Vancomycin is also recommended by mouth as a treatment for severe Clostridium difficile colitis. When taken by mouth it is very poorly absorbed.

Surface molecules

On its surface, N. gonorrhoeae bears hair-like pili, surface proteins with various functions, and sugars called lipooligosaccharides. The pili mediate adherence, movement, and DNA exchange. The Opa proteins interact with the immune system, as do the porins. Lipooligosaccharide (LOS) is an endotoxin that provokes an immune response. All are antigenic and all exhibit antigenic variation (see below). The pili exhibit the most variation. The pili, Opa proteins, porins, and even the LOS have mechanisms to inhibit the immune response, making asymptomatic infection possible. [13]

Dynamic polymeric protein filaments called type IV pili allow N. gonorrhoeae to adhere to and move along surfaces. To enter the host the bacteria uses the pili to adhere to and penetrate mucosal surfaces. [4] The pili are a necessary virulence factor for N. gonorrhoeae; without them, the bacterium is unable to cause infection. [8] To move, individual bacteria use their pili like a grappling hook: first, they are extended from the cell surface and attach to a substrate. Subsequent pilus retraction drags the cell forward. The resulting movement is referred to as twitching motility. [14] N. gonorrhoeae is able to pull 100,000 times its own weight, and the pili used to do so are the amongst the strongest biological motors known to date, exerting one nanonewton. [15] The PilF and PilT ATPase proteins are responsible for powering the extension and retraction of the type IV pilus, respectively. [16] [17] The adhesive functions of the gonococcal pilus play a role in microcolony aggregation and biofilm formation.

This illustration depicts a Gram stain of a urethral exudate showing typical intracellular Gram-negative diplococci, and pleomorphic extracellular Gram-negative organisms, which is diagnostic for gonococcal urethritis. Neisseria gonorrhoeae PHIL 3693 lores.jpg
This illustration depicts a Gram stain of a urethral exudate showing typical intracellular Gram-negative diplococci, and pleomorphic extracellular Gram-negative organisms, which is diagnostic for gonococcal urethritis.

Surface proteins called Opa proteins can be used to bind to receptors on immune cells and prevent an immune response. At least 12 Opa proteins are known and the many permutations of surface proteins make recognizing N. gonorrhoeae and mounting a defense by immune cells more difficult. [18]

Lipooligosaccharide (LOS) is a low-weight version of lipopolysaccharide present on the surfaces of most other Gram-negative bacteria. It is a sugar (saccharide) side chain attached to lipid A (thus "lipo-") in the outer membrane coating the cell wall of the bacteria. The root "oligo" refers to the fact that it is a few sugars shorter than the typical lipopolysaccharide. [4] As an endotoxin, LOS provokes inflammation. The shedding of LOS by the bacteria is responsible for local injury in, for example, pelvic inflammatory disease. [4] Although its main function is as an endotoxin, LOS may disguise itself with host sialic acid and block initiation of the complement cascade. [4]

Antigenic variation

N. gonorrhoeae evades the immune system through a process called antigenic variation. [19] This process allows N. gonorrhoeae to recombine its genes and alter the antigenic determinants (sites where antibodies bind), such as the Type IV pili, [20] that adorn its surface. [4] Simply stated, the chemical composition of molecules is changed due to changes at the genetic level. [7] N. gonorrhoeae is able to vary the composition of its pili, and LOS; of these, the pili exhibit the most antigenic variation due to chromosomal rearrangement. [8] [4] The PilS gene is an example of this ability to rearrange as its combination with the PilE gene is estimated to produce over 100 variants of the PilE protein. [21] These changes allow for adjustment to the differences in the local environment at the site of infection, evasion of recognition by targeted antibodies, and contribute to the lack of an effective vaccine. [21]

In addition to the ability to rearrange the genes it already has, it is also naturally competent to acquire new DNA (via plasmids), via its type IV pilus, specifically proteins Pil Q and Pil T. [22] These processes allow N. gonorrhoeae to acquire/spread new genes, disguise itself with different surface proteins, and prevent the development of immunological memory – an ability which has led to antibiotic resistance and has also impeded vaccine development. [23]

Phase variation

Phase variation is similar to antigenic variation, but instead of changes at the genetic level altering the composition of molecules, these genetic changes result in the turning on or off of a gene. [21] Phase variation most often arises from a frameshift in the expressed gene. [21] The Opacity, or Opa, proteins of N. gonorrhoeae rely strictly on phase variation. [21] Every time the bacteria replicate, they may switch multiple Opa proteins on or off through slipped-strand mispairing. That is, the bacteria introduce frameshift mutations that bring genes in or out of frame. The result is that different Opa genes are translated every time. [4] Pili are varied by antigenic variation, but also phase variation. [21] Frameshifts occur in both the pilE and pilC genes, effectively turning off the expression of pili in situations when they are not needed, such as after colonization when N. gonorrhoeae survives within cells as opposed to on their surfaces. [21]

Survival of gonococci

After gonococci invade and transcytose the host epithelial cells, they land in the submucosa, where neutrophils promptly consume them. [4] The pili and Opa proteins on the surface may interfere with phagocytosis, [8] but most gonococci end up in neutrophils. The exudates from infected individuals contain many neutrophils with ingested gonococci. Neutrophils release an oxidative burst of reactive oxygen species in their phagosomes to kill the gonococci. [24] However, a significant fraction of the gonococci can resist killing through the action of their catalase [4] which breaks down reactive oxygen species and is able to reproduce within the neutrophil phagosomes.

Stohl and Seifert showed that the bacterial RecA protein, which mediates repair of DNA damage, plays an important role in gonococcal survival. [25] Michod et al. have suggested that N. gonorrhoeae may replace DNA damaged in neutrophil phagosomes with DNA from neighboring gonococci. [26] The process in which recipient gonococci integrate DNA from neighboring gonococci into their genome is called transformation.

The growth of N. gonorrhoeae colonies on New York City agar, a specialized and selective medium for gonococci Neisseria gonorrhoeae Growth on New York City Agar Plate.jpg
The growth of N. gonorrhoeae colonies on New York City agar, a specialized and selective medium for gonococci

Genome

The genomes of several strains of N. gonorrhoeae have been sequenced. Most of them are about 2.1 Mb in size and encode 2,100 to 2,600 proteins (although most seem to be in the lower range). [27] For instance, strain NCCP11945 consists of one circular chromosome (2,232,025 bp) encoding 2,662 predicted open reading frames (ORFs) and one plasmid (4,153 bp) encoding 12 predicted ORFs. The estimated coding density over the entire genome is 87%, and the average G+C content is 52.4%, values that are similar to those of strain FA1090. The NCCP11945 genome encodes 54 tRNAs and four copies of 16S-23S-5S rRNA operons. [28]

Horizontal gene transfer

In 2011, researchers at Northwestern University found evidence of a human DNA fragment in a N. gonorrhoeae genome, the first example of horizontal gene transfer from humans to a bacterial pathogen. [29] [30]

Disease

Symptoms of infection with N. gonorrhoeae differ depending on the site of infection and many infections are asymptomatic independent of sex. [31] [13] [5] In symptomatic men, the primary symptom of genitourinary infection is urethritis – burning with urination (dysuria), increased urge to urinate, and a pus-like (purulent) discharge from the penis. The discharge may be foul smelling. [32] If untreated, scarring of the urethra may result in difficulty urinating. Infection may spread from the urethra in the penis to nearby structures, including the testicles (epididymitis/orchitis), or to the prostate (prostatitis). [32] [8] [33] Men who have had a gonorrhea infection have a significantly increased risk of having prostate cancer. [34] In symptomatic women, the primary symptoms of genitourinary infection are increased vaginal discharge, burning with urination (dysuria), increased urge to urinate, pain with intercourse, or menstrual abnormalities. Pelvic inflammatory disease results if N. gonorrhoeae ascends into the pelvic peritoneum (via the cervix, endometrium, and fallopian tubes). The resulting inflammation and scarring of the fallopian tubes can lead to infertility and increased risk of ectopic pregnancy. [32] Pelvic inflammatory disease develops in 10 to 20% of the females infected with N. gonorrhoeae. [32] It is important to note that depending on the route of transmission, N. gonorrhoeae may cause infection of the throat (pharyngitis) or infection of the anus/rectum (proctitis). [32] [8]

In perinatal infection, the primary manifestation is infection of the eye (neonatal conjunctivitis or ophthalmia neonatorum) when the newborn is exposed to N. gonorrhoeae in the birth canal. The eye infection can lead to corneal scarring or perforation, ultimately resulting in blindness. If the newborn is exposed during birth, conjunctivitis occurs within 2–5 days after birth and is severe. [32] [35] Gonococcal ophthalmia neonatorum, once common in newborns, is prevented by the application of erythromycin (antibiotic) gel to the eyes of babies at birth as a public health measure. Silver nitrate is no longer used in the United States. [35] [32]

Disseminated gonococcal infections can occur when N. gonorrhoeae enters the bloodstream, often spreading to the joints and causing a rash (dermatitis-arthritis syndrome). [32] Dermatitis-arthritis syndrome results in joint pain (arthritis), tendon inflammation (tenosynovitis), and painless non-pruritic (non-itchy) dermatitis. [8] Disseminated infection and pelvic inflammatory disease in women tend to begin after menses due to reflux during menses, facilitating spread. [32] In rare cases, disseminated infection may cause infection of the meninges of the brain and spinal cord (meningitis) or infection of the heart valves (endocarditis). [32] [35]

Transmission

N. gonorrhoeae may be transmitted through vaginal, oral, or anal sex; nonsexual transmission is unlikely in adult infection. [5] It can also be transmitted to the newborn during passage through the birth canal if the mother has untreated genitourinary infection. Given the high rate of asymptomatic infection, all pregnant women should be tested for gonorrhea infection. [5]

Traditionally, the bacterium was thought to move attached to spermatozoa, but this hypothesis did not explain female to male transmission of the disease. A recent study suggests that rather than "surf" on wiggling sperm, N. gonorrhoeae bacteria use pili to anchor onto proteins in the sperm and move through coital liquid. [36]

Infection

For N. gonorrhoeae, the first step after successful transmission is adherence to the epithelial cells found at the mucosal site that is infected. [37] The bacterium relies on type IV pili that attach and retract, pulling N. gonorrhoeae toward the epithelial membrane where its surface proteins, such as opacity proteins, can interact directly. [37] After adherence, N. gonorrhoeae replicates itself and forms microcolonies. [38] While colonizing, N. gonorrhoeae has the potential to transcytose across the epithelial barrier and work its way in to the bloodstream. [39] During growth and colonization, N. gonorrhoeae stimulates the release of cytokines and chemokines from host immune cells that are pro-inflammatory. [39] These pro-inflammatory molecules result in the recruitment of macrophages and neutrophils. [21] These phagocytic cells typically take in foreign pathogens and destroy them, but N. gonorrhoeae has evolved many mechanisms that allow it to survive within these immune cells and thwart the attempts at elimination. [21]

Prevention

Transmission can be reduced by using latex barriers (e.g. condoms or dental dams) during sex and by limiting sexual partners. [6] Condoms and dental dams should be used during oral and anal sex, as well. Spermicides, vaginal foams, and douches are not effective for prevention of transmission. [4]

Treatment

The current treatment recommended by the CDC is a dual antibiotic therapy. This includes an injected single dose of ceftriaxone (a third-generation cephalosporin) along with azithromycin administered orally. [40] Azithromycin is preferred for additional coverage of gonorrhea that may be resistant to cephalosporins but susceptible to macrolides. [41] [6] Sexual partners (defined by the CDC as sexual contact within the past 60 days) [11] should also be notified, tested, and treated. [6] [40] It is important that if symptoms persist after receiving treatment of N. gonorrhoeae infection, a reevaluation should be pursued. [40]

Antibiotic resistance

Antibiotic resistance in gonorrhea has been noted beginning in the 1940s. Gonorrhea was treated with penicillin, but doses had to be progressively increased to remain effective. By the 1970s, penicillin- and tetracycline-resistant gonorrhea emerged in the Pacific Basin. These resistant strains then spread to Hawaii, California, the rest of the United States, and Europe. Fluoroquinolones were the next line of defense, but soon resistance to this antibiotic emerged, as well. Since 2007, standard treatment has been third-generation cephalosporins, such as ceftriaxone, which are considered to be our "last line of defense". [42] [43]

Recently, a high-level ceftriaxone-resistant strain of gonorrhea called H041 was discovered in Japan. Lab tests found it to be resistant to high concentrations of ceftriaxone, as well as most of the other antibiotics tested. Within N. gonorrhoeae, genes exist that confer resistance to every single antibiotic used to cure gonorrhea, but thus far they do not coexist within a single gonococcus. However, because of N. gonorrhoeae's high affinity for horizontal gene transfer, antibiotic-resistant gonorrhea is seen as an emerging public health threat. [43]

Serum resistance

As a gram negative bacteria, N. gonorrhoeae requires defense mechanisms to protect itself against the complement system (or complement cascade), whose components are found with human serum. [44] There are three different pathways that activate this system however, they all result in the activation of complement protein 3 (C3). [45] A cleaved portion of this protein, C3a is deposited on pathogenic surfaces and results in opsonization as well as the downstream activation of the membrane attack complex. [45] N. gonorrhoeae has several mechanisms to avoid this action. [39] As a whole, these mechanisms are referred to as serum resistance. [39]

History

Name origin

Neisseria gonnorhoeae is named for Albert Neisser, who isolated it as the causative agent of the disease gonorrhea in 1878. [39] [3] Galen (130 AD) coined the term "gonorrhea" from the Greek gonos which means "seed" and rhoe which means "flow". [46] [7] Thus, gonorrhea means "flow of seed", a description referring to the white penile discharge, assumed to be semen, seen in male infection. [39]

Discovery

In 1878, Albert Neisser isolated and visualized N. gonorrhoeae diplococci in samples of pus from 35 men and women with the classic symptoms of genitourinary infection with gonorrhea – two of whom also had infections of the eyes. [21] In 1882, Leistikow and Loeffler were able to grow the organism in culture. [39] Then in 1883, Max Bockhart proved conclusively that the bacterium isolated by Albert Neisser was the causative agent of the disease known as gonorrhea by inoculating the penis of a healthy man with the bacteria. [21] The man developed the classic symptoms of gonorrhea days after, satisfying the last of Koch's postulates. Until this point, researchers debated whether syphilis and gonorrhea were manifestations of the same disease or two distinct entities. [47] [21] One such 18th-century researcher, John Hunter, tried to settle the debate in 1767 [21] by inoculating a man with pus taken from a patient with gonorrhea. He erroneously concluded that both syphilis and gonorrhea were indeed the same disease when the man developed the copper-colored rash that is classic for syphilis. [45] [47] Although many sources repeat that Hunter inoculated himself, [45] [39] others have argued that it was in fact another man. [48] After Hunter's experiment other scientists sought to disprove his conclusions by inoculating other male physicians, medical students, [39] and incarcerated men with gonorrheal pus, who all developed the burning and discharge of gonorrhea. One researcher, Ricord, took the initiative to perform 667 inoculations of gonorrheal pus on patients of a mental hospital, with zero cases of syphilis. [21] [39] Notably, the advent of penicillin in the 1940s made effective treatments for gonorrhea available.

See also

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Pilus

A pilus is a hair-like appendage found on the surface of many bacteria. The terms pilus and fimbria can be used interchangeably, although some researchers reserve the term pilus for the appendage required for bacterial conjugation. All pili in the latter sense are primarily composed of pilin proteins, which are oligomeric.

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<i>Neisseria meningitidis</i> species of bacterium

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Gonorrhea sexually transmitted infection

Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae. Many of those infected have no symptoms. Men may have burning with urination, discharge from the penis, or testicular pain. Women may have burning with urination, vaginal discharge, vaginal bleeding between periods, or pelvic pain. Complications in women include pelvic inflammatory disease and in men include inflammation of the epididymis. If untreated, gonorrhea can spread to joints or heart valves.

A pneumococcal infection is an infection caused by the bacterium Streptococcus pneumoniae, which is also called the pneumococcus. S. pneumoniae is a common member of the bacterial flora colonizing the nose and throat of 5–10% of healthy adults and 20–40% of healthy children. However, it is also a cause of significant disease, being a leading cause of pneumonia, bacterial meningitis, and sepsis. The World Health Organization estimate that in 2005 pneumococcal infections were responsible for the death of 1.6 million children worldwide.

Sortase

Sortase refers to a group of prokaryotic enzymes that modify surface proteins by recognizing and cleaving a carboxyl-terminal sorting signal. For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (Leu-Pro-any-Thr-Gly), then a highly hydrophobic transmembrane sequence, followed by a cluster of basic residues such as arginine. Cleavage occurs between the Thr and Gly, with transient attachment through the Thr residue to the active site Cys residue, followed by transpeptidation that attaches the protein covalently to cell wall components. Sortases occur in almost all Gram-positive bacteria and the occasional Gram-negative or Archaea, where cell wall LPXTG-mediated decoration has not been reported. Although sortase A, the "housekeeping" sortase, typically acts on many protein targets, other forms of sortase recognize variant forms of the cleavage motif, or that catalyze the assembly of pilins into pili.

Antibiotic resistance in gonorrhea

The Gonorrhea bacterium Neisseria gonorrhoeae has developed antibiotic resistance to many antibiotics.

Neisseria cinerea is a commensal species grouped with the Gram-negative, oxidase-positive, and catalase-positive diplococci. It was first classified as Micrococcus cinereus by Alexander von Lingelsheim in 1906. Using DNA hybridization, N. cinerea exhibits 50% similarity to Neisseria gonorrhoeae.

New York City agar

The N.Y.C medium or GC medium agar is used for isolating Gonococci.

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