Bacterial Pathogenesis and Virulence Part 2

Question 1

list and describe the 4 common ways bacteria evade host immune responses

Answer 1

1. capsule production: polysaccharide outermost covering of bacteria, mucoid, acts as a shield via
   1a. host mimicry: composition may mimic host polysaccharides
   1b. antiphagocytic: capsule viscosity and negative charge make it difficult for phagocytic cells to recognize and ingest
   1c. capsule prevents complement activation! by preventing binding of C3b (and other early initiators) to bacterial surface, may mask epitopes to interfere with antibody binding and classical complement activation, may mask mannose residues to interfere with mannose-lectin complement activation, also interferes with membrane attack complex formation
2. antigenic variation: changing expression of surface proteins while in host; now immune system has to start over and generate a whole new set of antibodies
3. catalase secretion: cleaves hydrogen peroxide produced by phagocyte during phagocytosis back to water and oxygen
4. survival within professional phagocytes: 4a. may inhibit phagosome fusion with lysosome to protect from enzymatic degradation; bacteria may reside and replicate within a modified phagosome
   4b. may escape phagosome before fusion with lysosome and enter cytosol, allowing bacteria to be protected from exposure to degradative enzymes

Question 2

explain the importance of iron to bacteria

Answer 2

iron essential for DNA synthesis, transcription, and cellular respiration as a cofactor in many enzymatic reactions and is REQUIRED for bacterial replication in the host

Question 3

explain how bacteria access iron in the host (2)

Answer 3

iron is abundant in nature but free iron concentration is low in the host bc most iron is bound to hemoglobin, lactoferrin, and transferrin; bacteria acquire it via:

1. bacteria have surface receptors for host iron-binding proteins; once bound, bacteria extract, internalize, and use the iron (magnet)
2. siderophores: produced and secreted by bacteria, small molecules with high affinity for iron that removes the iron from the host iron-binding protein and brings it to the siderophore receptor on bacteria surface, who removes and uses the iron (thief)

Question 4

list and explain the mechanism of action of the 3 types of bacterial toxins

Answer 4

1. membrane-dissolving toxins: host cell membrane is the target, where the toxin binds specific cell receptors (proteins, lipids, or carbohydrates) and disrupts the membrane integrity or inserts into the membrane to make a pore, causing cell contents to leak out; includes hemolysins (lyse RBCs, can release Hgb and snatch that sweet sweet iron), leukocidins (lyse plasma membrane of immune cells), and phospholipases (break down phospholipids in membranes)
2. AB toxins: A is active domain/enzymatic region and B is the binding domain (the part that binds to and mediates entry of toxin into host cell, often via endocytosis);
   the two domains separate after entry and A domain acts on its intracellular target, either disrupting protein synthesis (by targeting ribosomes) or disrupting host cell signaling
3. superantigens: these are secreted proteins that do not enter the cell, but instead bind and force the interaction of T helper cell receptors and MHC II molecules on APCs (independent of antigen specificity) and result in a robust T cell activation with massive cytokine release, resulting in a systemic inflammatory response