Neisseria, Bacteroides Flashcards
What are the characteristics of Neisseria sp.?
- Gram− diplococci
- Lipooligosaccharide (vs. LPS): lack O antigen extensions
- common oral flora and other mucous membranes
- pathogens: N.gonorrhoeae and N.meningitidis
- Host: only humans
Is there a vaccine for N. gonorrhoeae?
vaccination not possible
What are the virulence factors of N. gonorrhoeae?
- pili
- antigenic variation adhesions
- OPA
- IgA protease
- endotoxin
- phase variation
What allows for the antigenic variation in gonorrhea?
- PilE single chromosomal copy of pilin structural gene
- Strains contain 10-15 copies of PilE variants lacking promoter and 5-end of gene called PilS genes
- PilS genes recombine with PilE creating unlimited antigenic variants of PilE
- Result is that antigenic structure of pilus protein is constantly changing
What allows for phase variation for gonorrhea?
- on/off switch for surface protein expression
- In Neisseriae: Slipped Strand Mispairing resulting from presence of multiple identical repeated sequences at 5-end of gene. Replication errors due to strand misalignment creates reading frame errors.Often, premature stops, but also results in ON/OFF switch.
- Multiple Opa (Colony Opacity) protein copies scattered across genome; Slipped strand mispairing results in frequent variation in Opa protein expression or complete absence of Opa
What are the virulence factors for N. gonorrhoeae?
- pili
- IgA protease
- endotoxin
What are pili used for?
- mediate bacterial attachment to non-ciliated epithelia
- bacteria proliferate and shed into secretions
What are IgA proteases used for?
Usefulness of cleaving IgA: Coating of bacteria with IgA Fab fragments (does not activate complement and also blocks binding by other IgG and IgM)
What does shedding of endotoxins allow for?
secretion of pro-inflammatory cytokines
What do Serum-resistant virulent strains of N. gonorrhoeae cause?
disseminated gonococcal infections
- Strains lack Opa proteins (colony opacity proteins = outer-membrane proteins) Neutrophils unable to engulf bacteria lacking Opa proteins.
- Sialic acid on LOS (Lipidoligosaccharide of outer membrane) binds complement regulatory proteins, prevents complement-based phagocytosis
What does gonorrheal disease cause in men?
urethritis in men, urethral pus secretion (leukocytes with many gonococci)
What does gonorrheal disease cause in women?
cervicitis in women, frequently some urination sensitivity but no other symptoms
What can gonorrheal disease cause in neonatals?
Opthalmia Neonatorum
o destructive eye infection, acquired during birth
o Application of erythromycin ointment into both eyes of newborns is mandatory in many states and is considered standard neonatal care
What can gonorrheal disease lead to in women if it gets worse?
Pelvic Inflammatory Disease (PID) in women
- Initial infection of cervix, fallopian tubes and vaginal wall glands can lead to PID (15-30%):
- gonococci enter abdominal cavity, cause liver disease
- tissue scarring causes fallopian tube abnormalities which lead to ectopic pregnancies and sterility
What can gonorrheal disease lead to in men if it gets worse?
Urethral and testicular tubule scarring, resulting from epididymitis, leads to sterility and increased urethral infections by other microbes
What can disseminated gonococcal infection (without apparent genital infeciton) cause?
causes skin lesions, suppurative arthritis of a major joint, heart valve destruction
Once you get gonorrheal disease how suseptible are you to getting it again?
Little or no protective immunity (pilin variability!) is observed after recovery from an infection with N.gonorrhoeae.
What is a very important fact of neisseria meningitidis that makes it so deadly?
- crosses the blood-brain barrier
What are the factors of neisseria meningitidis that affect intrvascular survival?
- capsule
- acquisition of iron from transferrin
What are the symptoms of neisseria meningitidis?
- mild cold, progress to throbbing headache, fever, stiffness in neck and back, nausea and vomiting, deafness and coma
- Shock and death (100% if untreated) may occur within 24 hours, but frequently is slower so that effective treatment can be given (<10% death in treated
cases).
What are the reasons for death due to Neisseria meningitidis?
- Obstruction of release of increased fluid pressure (due to PMN attempts at eradication: pus and clotting) impairs brain, causes paralysis of motor nerves and coma. Loss of blood supply to brain is one of the frequent symptoms just prior to death
- LOS/endotoxin release from blood-circulating meningococci (which have a high tendency to auto-lyse and thus spread LOS widely) causes shock
How can you tell a Neisseria meningitidis infection from other types of meningitis?
small local skin hemorrhages are observed: Localized loss of vascular integrity: effect of inflammatory cytokines release induced by endotoxin activation of macrophages
What is purpura fulminans that occurs in Neisseria meningitids?
blood spots, bruising, and discoloration of skin from coagulation in small blood vessels
What can purpura fulminans progress to in a Neisseria meningitidis infection?
disseminated intravascular coagulation: blood clots throughout the circulatory system resulting in blockages and excessive bleeding elsewhere (clotting factors depleted)
What are the virulence factors of N. meningitidis?
- polysaccharide capsule
- endotoxin
- pili
- IgA protease
What are the two effective vaccinations against capsular polysaccharides?
MenACWY Vaccine – Protection from 4 major disease-causing strains: A, C, W135 and Y (serotyping: 12 antigenic groups)
MenB vaccine – B capsule poly-sialic acid
What are the clinical features of N. gonorrhoeae?
- gonorrhea
- pelvic inflammatory disease
- arthiritis
What are the clinical features of N. meningitidis?
- meningitis
- meningococcemia
What is the epidemiology of N. gonorrhoeae?
- sexual transmission
- asymptomatic carrier
What is the epidemiology of N. meningitidis?
- asymptomatic carrier
- aerosol transmission
- children/young adults
What are the virulence factors for bacteroidales?
- superoxide dismutase
- catalase
- polysaccharide capsule
What are the characteristics of bacteroidales?
- gram -
- strict anaerobes
- commensals
- opportunistic pathogens
What is bacteroides fragilis?
-most frequently isolated from clinical specimens of abscesses caused by intestinal bacteria
-most oxygen-resistant Bacteroides
What disease is caused by bacteroidales?
Disease caused when bacteria are introduced into deep tissues
- peritonitis - rupture of infected appendix/diverticulum
- pulmonary abscess - aspiration of oropharyngeal bacteria
What does bacteroides fragilis cause in disease?
- biphasic - start with acute inflammation and progress to formation of localized abscesses
- bacterial composition changes as disease progresses;100’s of different species in inoculum and few species in abscess
What is the course of a bacteroidales disease?
- perforation of intestine/spillage of intestinal fluid
- neutrophils mobilized
- surviving bacteria resistant to phagocytosis: B. fragilis has a capsule
- oxygen-sensitive bacteria are killed
peritoneal cavity well-oxygenated - facultative anaerobes grow first (E. coli)
- some strict anaerobes survive
- site becomes anaerobic
- surviving strict anaerobes become predominant
How do you treat bacteroidales?
treat with Surgery and antibiotic combinations (target aerobes and anaerobes)