Neisseria & Bacteroides Flashcards
Neisseria sp. • Gram? shape? • LPS? • common where? • O2 use? • pathogenic species? Host?
• Gram− diplococci
• Lipooligosaccharide (vs. LPS): lack O antigen extensions
• common oral flora and other mucous membranes
• facultative anaerobe
• pathogens: N.gonorrhoeae and N.meningitidis
Host: only humans
Virulence Factors of N. gonorrhoeae
Ag variation (pilin) phase variation pili IgA protease lack of Opa sialic acid on LOS shedding of endotoxin
antigenic variation of pilin
Gonococci at different infection sites in an infected individual often express different pilin genes
because they adhere to different cell surface receptors on distinct mucosal epithelial cells.
ØPilE single chromosomal copy of pilin structural gene
ØStrains contain 10-15 copies of PilE variants lacking promoter and 5-end
of gene called PilS genes
ØPilS genes recombine with PilE creating unlimited antigenic variants of PilE
ØResult is that antigenic structure of pilus protein is constantly changing
phase variaiton
nassiera and E.coli
effects on Opa expression
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
E. coli and other Gm- rods simple inversion of promoter
N. Gon surface attachment
Pili mediate bacterial attachment to non-ciliated epithelia
bacteria proliferate and shed into secretions;
Does N. Gon have a capsule
no
IgA protease of N. gon, how can cleaved IgA be useful
Usefulness of cleaving IgA: Coating of bacteria with IgAFab fragments (does not activate complement and also blocks binding by other IgG and IgM)
Serum-resistant virulent strains cause:?
disseminated gonococcal infections:
Serum-resistant virulent strains
lack what protein/ significance?
how do they avoid phago?
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
endotoxin shedding of n. gon
Shedding of lots of endotoxin (LOS of these bacteria, LIPID A) Binds TLR-4 (especially on dendritic cells, macrophage & B cells) secretion of pro-inflammatory cytokines that can lead to shock
Gonorrheal Diseases diseases via Sexual transmission
urogenital infections
§ Frequently (almost) asymptomatic
o urethritis in men, urethral pus secretion (leukocytes with many gonococci)
o cervicitis in women, frequently some urination sensitivity but no other symptoms
(infection tracing is important to prevent re-infection)
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
Pelvic Inflammatory Disease (PID) in women
future impacts?
Initial infection of cervix, fallopian tubes and vaginal wall glands can lead to PID (15-30%):
o gonococci enter abdominal cavity, cause liver disease
o tissue scarring causes fallopian tube abnormalities which lead to ectopic pregnancies
and sterility
Urethral and testicular tubule scarring caused by and can lead to?
resulting from epididymitis
leads to sterility and increased urethral infections by other microbes
Disseminated Gonococcal Infection (without apparent genital infection) causes:
skin lesions, suppurative arthritis of a major joint, and heart valve destruction.
N. gon resistance
Antibiotic resistance for penicillin and tetracyclin is widespread.
USA: Sensitivity for fluoroquinolones and cephalosporins: >95%
Worldwide: significant rise in resistance.
protective immunity after n. gon infection?
Little or no protective immunity (pilin variability!) is observed after recovery from an infection with N.gonorrhoeae.
Neisseria meningitidis age group
children to college aged
Neisseria meningitidis carriers/ transmission
10% of healthy people are carriers of bacteria
Sputum transmission
symptoms onset of Neisseria meningitidis infection
untreated vs treated?
Symptoms start like a 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 frequentlyis slower so that effective treatment can be given (<10% death in treated cases)
Neisseria meningitidis infection increased fluid pressure?
Obstruction of release of increased fluid pressure (due to PMN attempts at eradication: pus and clotting) impairs brain, causes paralysis of motor nervesand coma.
Loss of blood supply to brain is one of the frequent symptoms just prior to death
Neisseria meningitidis induced shock
LOS/endotoxin release from blood-circulating meningococci (which have a high tendency to auto-lyse and thus spread LOS widely) causes shock (inflam cytokine release)
can spread in blood due to capsule
skin lesions of Neisseria meningitidis infection
progression?
small local skin hemorrhages are observed: Localized loss of vascular integrity: effect of inflammatory cytokines release induced by endotoxin activation of macrophages.
Purpura fulminans: blood spots, bruising, and discoloration of skin from coagulation in small blood vessels
Can progress to disseminated intravascular coagulation: blood clots throughout the circulatory system resulting in blockages and excessive bleeding elsewhere (clotting factors depleted)
Virulence Factors of N.meningitidis
Ø Large capsule leads to disseminated intravascular coagulation (DIC)
Some virulent strains have capsules with sialic acid on LOS (like N.gonorrhea): reduces phagocytosis further
Ø IgA protease
Ø Pili
Ø Shedding of lots of Endotoxin via LOS =shock
vax for N.meningitidis
Effective vaccination against capsular polysaccharides
MenACWY Vaccine – Protection from 4 major disease-causing strains:
A, C, W135 and Y (serotyping: 12 antigenic groups)
MenB vaccine – also recommended for B capsule poly-sialic acid;
typically mandatory vax for any group living situations
Neisseria
gram
shape
O2 use
gram -
cocci
strict aerobes
N.meningitidis epidemilogy
asymptomatic carriers via aerosols to children/ young adults
N.gonorrhoeae epidemiology
sexual transmission
asymptomatic carrier
Bacteroidales: gram where found O2 use pathogenic
Gram− bacteria of the human colon/oral cavity Strict anaerobes Commensals Opportunistic pathogens
Bacteroides fragilis
- most frequently isolated from?
- O2 resistance?
- most frequently isolated from clinical specimens of abscesses caused by intestinal bacteria
- most oxygen-resistant Bacteroides
Bacteroidales virulence factors
Ø Superoxide dismutase - detoxifies oxygen radicals
Ø Catalase - breaks down hydrogen peroxide
Ø Polysaccharide capsule
Bacteroidales Superoxide dismutase and Catalase allow for?
Allows survival in well oxygenated peritoneal cavity
Also helps bacteria resisting killing by phagocytosis
Bacteroidales disease caused when?
types?
caused when bacteria are introduced into deep tissues
- peritonitis - rupture of infected appendix/diverticulum
- pulmonary abscess - aspiration of oropharyngeal bacteria
Bacteroidales diseases major bacteria? only one bacteria? phases of disease? species numbers?
Bacteroides fragilis is one component in these diseases, polymicrobial diseases
biphasic - start with acute inflammation and progresses to the formation of localized abscesses
bacterial composition changes as disease progresses
100’s of different species in inoculum
few species in abscess: due to response of the host and features of individual bacterial
species
Abscess what is it? Does development involve factors from host/bacteria? how it forms? when can they be problematic?
local collection of pus
Development involves both bacteria and host factors
Early: acute inflammatory response (neutrophils), Some neutrophils lysed by bacteria (neutrophil contents damaging)
Host surrounds area with thick-walled fibrin capsule
Blood supply is cut off
The Center of abscess is necrotic: Dead neutrophils, dead and live bacteria, and Edema fluid
Problems if abscess located in a vital area of the body OR if the abscess BURSTS!
Course of Bacteroides disease in intestine, treatment
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
treat with Surgery and antibiotic combinations (target aerobes and anaerobes)
