8 Flashcards
Neisseria
The only genus of Gram negative cocci that frequently cause disease
• Usually diplococcic
• N. gonorrhoeae (gonorrhea)
• N. menigitidis (bacterial meningitis and septicemia)
• Non-motile (twitching motility from pili)
• Aerobes (but can grow anaerobically)
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• Grow best in on media supplemented with blood in presence of CO2
• Obligate human pathogens
• Fragile, do not survive long outside host • Humans are only reservoirs
Diagnosis Neisseria
Culture on chocolate agar in presence of CO2 • Boiled blood, iron, vitamins
• Colonies = nonpigmented, mucoid, non-hemolytic
• Modified Thayer-Martin agar (MTM) • Indicative of antibiotic resistance
• Positive for Catalase and Oxidase • Sugar Fermentation
• Meningococci – ferment glucose and maltose, but not sucrose or lactose
• Gonococci – ferment glucose, but not maltose or sucrose
Two Major Neisseria sp.
N. meningitidis
(Meningococcus)
N. gonorrhoeae
(Gonococcus)
N. men… Habitat
Throat; Human nasopharynx is the only known reservoir for N meningitidis
N. gon… Habitat
Mucosal epithelia of male urethra or female cervix
Encounter n. men
Spread by airborne droplets. Viral respiratory infections (e.g., influenza) may enhance the spread.
N. gon. Encounter
Contact with genital secretions
Virulence factors n. men
Large capsule,
Outer membrane blebs
- LPS endotoxin Hemolysin
Virulence factors n. gon
No capsule
Pili and strong adhesins LPS endotoxin
IgA1 protease Phase/antigenic variation
N. men Diseases
Septicemia, Meningitis, Purpura fulminans
N. gon Diseases
Disseminated Gonococcal Infection (DGI), Pelvic Inflammatory Disease (PID),Urethritis/cervitis/epididymitis
N. men Infection site and characteristics
Upper respiratory and meninges
Ranges from transient bacteremias that are relatively benign to overwhelming infections that are rapidly fatal
N. gon Infection site and characteristics
Genitals
Localized, bacteremia rarely lethal
Encounter and Entry - Meningococci
Human nasopharynx – primary reservoir for N. meningitidis, has also been found in dental plaque
• Attach to nasopharyngeal epithelial cells and invade mucous membranes
• Asymptomatic carriage induces humoral antibody response • Most individuals acquire immunity by age 20
• Invasion of the blood stream only occurs in individuals deficient in complement component (C5 - C8)
• Once in blood stream, travel through body
• Type IV pili - attach organism to meninges in CNS
• Lipooligosaccharide (LOS) damages host tissue
• Elicits host inflammatory response, resulting in hemorrhaging of blood into skin and mucous membranes (purpuric rash)
Encounter and Entry - Gonococci
Human are the only reservoirs
• Colonizes cervix in women or distal urethra in both sexes • Asymptomatic carriers greater among women
• Upon introduction, attach to columnar epithelia of cervix or urethra
• Pili and surface proteins
• Adhesins controlled by:
• Phase variation – presence/absence • Antigenic variation - composition
Spread and Multiplication
Gonococci multiply rapidly
• Shed in genital secretions
• Do not have flagella and are not motile • Can enter epithelial cells
• Extracellular protease cleaves IgA1
• Removes Fc-receptor end of antibody
• Enables escape from phagocytosis?
• Haemophilus and streptococci also possess
Attachment to non-ciliated cells
• Human fallopian tubes and columnar epithelial cells have ciliated and non-ciliated cells
• Non-ciliated cells have microvilli • Ciliary stasis
• Ciliated cell motility slows and ceases
• Death of ciliated cells
• Slough from epithelial surface
• Can be elicited by LPS and peptidoglycan
Internalization
• Non-ciliated microvilli engulf
bacteria
• Internalized by “parasite directed endocytosis”
- Intracellular replication (protection) • Gonococci may multiply within vacuoles
- Intracellular traffic
- Vacuoles fuse with basement membrane
Exocytosis
• Vacuoles discharge bacteria into subepithelial connective tissue
Damage - gonorrhea
Do not secrete exotoxins
• LPS (LOS – lipooligosaccharide) and other cell wall
components cause cell damage
• Induce tumor necrosis factor-alpha (TNF-α)
• Sloughing of ciliated cells
• Non-ciliated cell lysis – release of factors that cause inflammation
Survival gonorrhea
Serum antibodies recognition
• Target: LPS (LOS), Protein I of the outer membrane (OM)
and other surface proteins
• N. meningitidis divided into serogroups A, B, C, W135, X, Y, and Z, depending on group-specific capsular polysaccharide antigens
• Evasion
• Strains alter LPS with host-derived N-acetylneuraminic
acid (sialic acid)
• Surface component of red blood cells (camouflage)
• LOS is similar to antigens on human erythrocytes and may allow ‘self’ recognition
Neisseria Infections - • Gonococci
Localized inflammation
• Rarely lethal (even with spread to bloodstream)
Meningococci neisseria infections
Colonize nasopharynx with no local symptoms • Three general diseases:
1. 2. 3.
Uncomplicated bacteremic process Metastatic infection of the meninges
Overwhelming systemic infection - circulatory collapse and disseminated intravascular coagulation (DIC)
• Individuals may lack IgG antibodies that have specificity for the capsular polysaccharide
• Highest known bacterial titers in blood
• Virulence Factor Differences
• Meningococci heavily encapsulated (polysaccharide) and produces hemolysin
Pelvic Inflammatory Disease (PID)
Gonococcal infection of female upper reproductive tract • Inflammation of uterus and fallopian tubes
• Scarring of upper tract and adjacent organs
• Infertility
• Ectopic pregnancy – development of embryo in fallopian tube rather
than uterus
• Chronic pelvic pain
• Epididymitis
• Ascent of organism into upper reproductive tract of men
Disseminated Gonococcal Infections
Disseminated gonococcal infections (DGI) • Can result from PID due to endotoxin • Pustular lesions of skin • Inflammation of tendons and joints • Suppurative arthritis • More common in women
Purpura Fulminans - Meningococcus
• Disseminated intravascular coagulation (DIC) due to ability to survive in bloodstream
• Skin manifestations • Meningitis
• Shock
• Death
• Response to LOS mediated by TNF-α and IL-1
• The higher the response, the greater the damage and
risk of death