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Chapter 14 Neisseriae Learning Objectives 1. How are gonococci (N. gonorrhoeae) spread? What is the resevoir of infection? Only via person-to-person contact; they do not persist in the environment Asymptomatic carriers of both genders, although mostly women 2. What three factors enable gonococci to attach to host cells? Why don’t antibodies prevent infection? A lack of what protein allows them to resist phagocytosis? Pili, lipooligosaccharide (LOS/endotoxin, a variant of LPS), and some other surface proteins Gonococci use both phase variation and antigenic variation Lack of Opa (colony Opacity-associated proteins) 3. How does antigenic variation work? How does phase variation differ? What is a special type of phase variation? Homologous recombination between a complete (active) locus and several silent alleles i. Used for the pilin gene, which encodes pili proteins A single locus is turned on and off rapidly, often via inversion of the promoter region i. Special: gonococci use slippped strand mispairing on Opa, which uses gains and losses of CTCTT sequences to form stop codons and oscillate gene expression 4. 5. What are the phases of cell attack in a N. gonorrhoeae infection (7)? 1) Attachment to nonciliated cells, (2) cilliary stasis, (3) death of ciliated cells, (4) internalization by nonciliated cells (“nonprofessional phagocytes”), (5) replication within vacuoles, (6) intracellular traffic, and finally (7) exocytosis into either blood or subepithelial connective tissue What host-derived molecule causes death and sloughing of ciliary epitheliumin in particular? TNF-α, produced in response to peptidoglycan and LPS [tissue necrosis factor] 6. What immune systems are necessary to fight off gonococci? What are their 2 main targets? Complement and IgG & IgM antibodies Target LOS and protein I i. However LOS may be altered by addition of sialic acid and rendered invisible 7. Why are cultures of blood, joint fluid, or skin lesions often sterile (3)? Low numbers Weird nutritional requirements In tenosynovitis, inflammation is due to deposition of immune complexesand antibodies rather than actual gonococci 8. 9. Which species of Neiseria has a capsule? N. meningitidis What are four signs of the entry of meningococci (N. meningitidis) into the bloodstream? With what two molecules does the likelihood of death correlate best? Purpura fulminans, DIC, meningitis, shock Endotoxin and TNF-α levels 10. Which meningococcus serogroup can we not be immunized for? Serogroup B’s capsule resembles the host 11. What three agar plates can grow gonococci? Chocolate agar, Use these two if there are other bacteria or yeasts, usually normal flora, that need to be suppressed: i. Thayer-Martin medium ii. Martin-Lewis medium 12. What test can determine if you have any Neisseria? How can you narrow down species? Oxidase reagent test (Neisseria turn purple) N. gonorrhoeae eat only glucose N. meningitidis eat glucose and maltose 13. What’s the first pharmacological line of defense for Neisseriae? [discounting the vaccine for most of N. meningitidis!] Cephalosporins: cefixime (PO) or ceftriaxone (IM), b/c of rampant β-lactamases Assume concurrent chlamydia infection and treat with azithromycin or doxycycline