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44 Cards in this Set
- Front
- Back
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What is Neisseria gonorrhoeae?
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It is an example of a pathogen that uses adherence and antigenic variation to avoid the host's immune system.
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Describe Neisseria gonorrhoeae.
The physical characteristics |
1) Non-motile, non-sporulating Gram negative cocci
2) Seen in pairs with adjacent sides flattened 3) Do not survive in environment, spread only occurs by direct contact since bacteria are fragile |
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What are main virulence factors of Neisseria gonorrhoeae?
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1) Adhesins
2) Antigenic variation 3) Resistance to the killing action of the membrane attack complex of complement 4) Iron Acquisition studies |
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What is the disease caused by Neisseria gonorrhoeae?
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-It is a strictly human pathogen and is the causative agent of Gonorrhea
-Sexually Transmitted Disease -Many cases go asymptomatic and undiagnosed |
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How does Neisseria gonorrhoeae enter the body of males?
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By the way of mucous membranes of the genitourinary trat.
In males, Neisseria gonorrhoeae causes urethritis (inflammation of the urethra) and may include symptoms such as painful or difficult urination or maybe asymptomatic |
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How does Neisseria gonorrhoeae enter the body of females?
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It enters the mucous membranes lining the cervical canal, thus the primary infection is present in the endocervix (also infection could be possible in urethra)
-Symptoms - include cervical vaginal discharge, painful or difficult urination etc -Could be asymptomatic -Major complication of untreated gonorrhea in women is dissemination into uterus and fallopian tubes causing pelvic inflammatory disease (PID) -causes sterility in woman and hronic pelvic pain |
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dissemination
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diffused
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In ___ of cases the bacteria can become more disseminated in the body causing diseases such as gonococcal arthritis
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3%
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How does N. gonorrhoea cause disease?
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It induces inflammation and avoiding acquired immune response through antigentic variation
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How effective are the treatments to N. gonorrhoea?
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Recovery is fast with antibiotics
-If left untreated, eventually most cases of uncomplicated gonorrhea will clear and the person fully recovers on their own after approximately 6 months |
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What is a risk that infected women have?
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Women who are infected with N. gonorrhoeae can transmit the bacteria into the eyes of their infants during birth
-Infection of the eyes of the infant can cause corneal damage and possibly blindness, a condition called ophthalmia neonatorum -This is prevented by the routine use of antibacterial eye drops (silver nitrate or antibiotics) by hospitals |
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What are the three techniques used to diagnose gonorrhea?
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1) Microscopy
2) Culture 3) DNA |
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Explain how microscopy can be used to diagnose gonorrhea?
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-Sample of urethral or cervical discharge is smeared on glass slides and stained by Gram strain procedure
-Presence of gram-negative diplococci within neutrophils is usually indicative of a gonorrhea infection -Gram-negative diplococci are not typically part of the normal flora of the genitourinary tract -This test will confirm the diagnosis of gonorrhea in most male patients |
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Explain how culture can be used to diagnose gonorrhea?
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-Sapmle of discharge is spread onto a special media that inhibits the growth of the normal flora bacteria and incubated for 48 hours
-Standard biochemical tests such as sugar fermentation or the detection of oxidase enzyme, as well as cell and colony morphologies can be used to identify the bacterium -laboratory culture of the bacterium is then done to conifirm the identity of the pathogen and for diagonsis in asymptomatic individuals (Many female patients will have a positive culture result but a negative cervical gram-stain result for N gonorrhoeae) |
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Explain how DNA can be used to diagnose gonorrhea?
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Nucleic acid based detected test can be used to detect the presence of bacterial genes in urine samples or cervical swabs
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N. gonorrhoeae specially adheres to genitourinary tissues. How does it do it?
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N. gonorrhoeae uses pili and other surface proteins to attach to host cells and remain attached despite the periodic flow of urine
-Pili are polymers of thousands of protein subunits called PilE proteins or pilin |
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What are the pili?
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They are polymers of thousands of protein subunits called PilE proteins or pilin
-At tip of pili is another protein, PilC which functions as an adhesin and mediates adherence to the urethral or cervical epithelial cells, thereby enhancing the bacterium's ability to cause disease |
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What happens after the bacteria has adhered to the surface of the urethral or cervical epithelial cells?
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1) bacteria are ingested by epithelial cell
2) Transcytose (macromolecules transported to interior of cell) through the cell and enter into the subepithelial space 3) Host body mounts an inflammatory response which is responsible for most of the symptoms of gonorrhea |
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What is Opa?
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Opa are outer membrane proteins.
-They stand for opacity-associated proteins -THeir exprssion causes colonies of N. gonorrhoeae grown on agar to appear opague -They play a role in the bacterium's ability to invade host cells |
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What kind of an immune response does infection with N. gonorrhoeae stimulate?
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It stimulates inflammation and a local immune IgA response
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What is a risk that infected women have?
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Women who are infected with N. gonorrhoeae can transmit the bacteria into the eyes of their infants during birth
-Infection of the eyes of the infant can cause corneal damage and possibly blindness, a condition called ophthalmia neonatorum -This is prevented by the routine use of antibacterial eye drops (silver nitrate or antibiotics) by hospitals |
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What are the three techniques used to diagnose gonorrhea?
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1) Microscopy
2) Culture 3) DNA |
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Explain how microscopy can be used to diagnose gonorrhea?
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-Sample of urethral or cervical discharge is smeared on glass slides and stained by Gram strain procedure
-Presence of gram-negative diplococci within neutrophils is usually indicative of a gonorrhea infection -Gram-negative diplococci are not typically part of the normal flora of the genitourinary tract -This test will confirm the diagnosis of gonorrhea in most male patients |
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Explain how culture can be used to diagnose gonorrhea?
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-Sapmle of discharge is spread onto a special media that inhibits the growth of the normal flora bacteria and incubated for 48 hours
-Standard biochemical tests such as sugar fermentation or the detection of oxidase enzyme, as well as cell and colony morphologies can be used to identify the bacterium -laboratory culture of the bacterium is then done to conifirm the identity of the pathogen and for diagonsis in asymptomatic individuals (Many female patients will have a positive culture result but a negative cervical gram-stain result for N gonorrhoeae) |
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Explain how DNA can be used to diagnose gonorrhea?
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Nucleic acid based detected test can be used to detect the presence of bacterial genes in urine samples or cervical swabs
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N. gonorrhoeae specially adheres to genitourinary tissues. How does it do it?
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N. gonorrhoeae uses pili and other surface proteins to attach to host cells and remain attached despite the periodic flow of urine
-Pili are polymers of thousands of protein subunits called PilE proteins or pilin |
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What are the pili?
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They are polymers of thousands of protein subunits called PilE proteins or pilin
-At tip of pili is another protein, PilC which functions as an adhesin and mediates adherence to the urethral or cervical epithelial cells, thereby enhancing the bacterium's ability to cause disease |
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What happens after the bacteria has adhered to the surface of the urethral or cervical epithelial cells?
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1) bacteria are ingested by epithelial cell
2) Transcytose (macromolecules transported to interior of cell) through the cell and enter into the subepithelial space 3) Host body mounts an inflammatory response which is responsible for most of the symptoms of gonorrhea |
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What is Opa?
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Opa are outer membrane proteins.
-They stand for opacity-associated proteins -THeir exprssion causes colonies of N. gonorrhoeae grown on agar to appear opague -They play a role in the bacterium's ability to invade host cells |
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What kind of an immune response does infection with N. gonorrhoeae stimulate?
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It stimulates inflammation and a local immune IgA response
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What is one way that N. gonorrhoeae invade the immune response?
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To undergo antigenic variation
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What is antigenic variation?
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It results from gene rearrangements in the DNA that take place at high frequency
-Variants that have changes in the structure of a surface molecule can then evade the host's antibody response |
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How does N. gonorrhoeae achieve antigenic variation?
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-Chromosome contains a single complete copy of the pilin gene called pilE for pilin expression locus
-There are 10 to 15 copies of variant-encoding pilin genes -Each of the variant-encoding genes is truncated (cut short) at the 5' end and lacks a promoter region and the sequences encoding the N-terminal portion of the pilin protein -These variant-encoding genes are called pilS for silent (non functional) loci -Therefore antigenic variation occurs predominately in the C-terminal region of pilin The N-terminal region of pilin is highly conserved |
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Why does antigenic variation occur?
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It occurs when the genetic information in a pilS gene is transferred to the complete gene by homologous recombination
-Small stretches within a pilS gene can be recombined into the pilin expression locus resulting in chimeric pilin types -This provides the bacterium with a mechanism to produce approximately one million different antgienic variants -Antigenic variation can occur frequently -For exmaple a single bacterium can switch to one copy, then to another copy and then back to the original copy of the gene all over the course of one infection |
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How many copies of the pilC and opa genes does N. gonorrhoeae possess?
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It has two copies of the pilC gene (pilC1 and pilC2)
-It has 10 or more copies of opa genes |
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What is the function of the PilC protein?
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It is necessary for proper assembly and maturation of the pili
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What is the function of the Opa proteins?
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The different Opa proteins may enable the bacterium to adhere to a variety of host cell types
-Some of the Opa proteins seem to be important in bacterium-neutrophil interactions, even in the absence of antibodies -Once phagocytosed, the bacteria are killed by both oxygen dependent and independent mechansims -Mutants lacking Opa proteins are not engulfed by neutrophils and have been implicated with PID and gonococcal arthritis |
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How can N. gonorrhoeae vary the amount of pili and Opa proteins expressed at the cell surface?
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-Expression of the pilE gene is controlled at the level of transcription by a regulatory system allowing the bacterium to switch between Pil+ and Pil-
-At any particular time the bacterium may express zero, one, or several different Opa proteins -Process of turning on or off the expression of a particular gene product is called phase variation |
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How do we treat N. gonorrhoeae infections?
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-Penicillin and tetracycline used to be effective treatments but bacteria gained resistance by acquiring plasmids encoding resistance
-Thus penicillin and tetracycline are no longer recommended in treatment in Canada -Thus we use other drugs like ciprofloxacin, but the bacteria are gaining resistance to these drugs too |
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Does Vaccination work against N. gonorrhoeae?
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-Although people infected with N. gonorrhoeae mount an antibody response to the pili and other surface proteins, there is no acquired immunity after infection
-Therefore it is possible that previously infected people can be re-infected -Since pili are major virulence factor of N. gonorrhoeae, there have been many attemps to produce a vaccine on this surface antigen -Success has been thwarted by extensive antigenic variation of pillin -Vaccine development has been hampered by lack of suitable animal model |
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How can we prevent N. gonorrhoeae infections?
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1) Condoms
2) Contact tracing |
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Contact Tracing
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Used to identify contacts who were exposed to the index patient and who may have become inflected
-useful in dealing with asymptomatic individuals |
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How can we prevent N. gonorrhoeae infections?
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1) Condoms
2) Contact tracing |
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Contact Tracing
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Used to identify contacts who were exposed to the index patient and who may have become inflected
-useful in dealing with asymptomatic individuals |
