10-14-09 Bacterial Pathogenesis 1. Describe the transmission routes for bacteria.

Human-to-human: The two most common transmission routes are airborne respiratory droplets and fecal-oral. Other transmission routes include sexual contact, urine, skin, blood transfusion, insect bites, and contaminated needles. Vertical transmission can occur from mother to child, either transplacentally, through the birth canal, or through breast milk. Non-human-to-human: Soil, water, animals*, or fomite sources. *When animals are the source of pathogens, they are called reservoirs. Diseases from which animals are the source are called zoonoses. *When animals are the mode of transmission, they are called vectors. 2. Contrast intracellular and extracellular bacteria. Intracellular bacteria can form granulomas, which are composed of a core of multinucleated giant cells (from fusion of infected macrophages) surrounded by a border of T cells. Such bacteriaMycobacterium, Legionella, Brucella, and Listeriaprefer residing intracellularly to protect themselves from antibodies and neutrophils. To eliminate intracellular bacteria, TH1 helper cells are needed (think HIV!). Extracellular bacteriasuch as Pseudomonas aeruginosaorganize into biofilms via quorum sensing, or the communication mechs used for collective behavior. A dental plaque is an example of a biofilm. The biofilm can protect bacteria from host defenses and antibiotics. 3. Discuss mechanisms of evasion of host defenses by bacteria. evading recognition and killing by phagocytic cells by: a. destroying the phagocyte (i.e. using leukocidin) b. preventing phagosome lysosome fusion c. escape from phagolysosome d. resistance to acidification and production of toxic substances within the phagolysosome (i.e. with a capsule) 2. inactivating or evading the complement system and antibodies by: a. varying the structure of surface antigens to evade antibody response b. produce protease to degrade IgA c. limit the chemotaxis of leukocytes by degrading C5a d. make an IgG binding protein called protein A (prevents opsinization of the bacteria with IgG, thus blocking complement) e. the O Antigen of gram negative LPS prevents complement from gaining access to the membrane and therefore inhibits activation of the compelement cascase
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biofilm can prevent antibodies and complement from getting into the bacteria 3. grow intracellularly a. bacteria such as mycobacteria, francisellae, brucellae, chlamydiae, and rickettsiae can grow inside cells facultatiely or obligately, evading antibodies and complement. TH1 helper cells can elicit immune response against them.
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4. Discuss virulence factors Virulence factors are the characteristics and features of an organism that contribute to its pathogenicity. They include pili: bacterial pili contain adhesins on their tips, which bind to receptors on the epithelial cell surface allowing for entry into the human body. Capsules: capsules serve two purposes. Firstly, they are poorly antigenic, which allow the bacteria to evade recognition. A capsule-specific antibody is often required for phagocytosis to occur. Secondly, the capsule is antiphagocytic, making it difficult to be ingested. Other properties include protecting the bacteria from dessication, viruses and detergents. Exotoxins: polypeptides that can be produced by both gram positive and gram negative bacteria. The toxin is often encoded in a lysogenic phage and appear as dimeric A-B toxins. The B subunit binds to a specific cell surface receptor, while the A subunit is transferred into the interior of the cell, causing injury. Exotoxin is secreted. Endotoxins: basically, endotoxin is LPS, which is a lipopolysaccharide that is only produced by gram negative bacteria. Its primary function is to initiate systemic inflammatory responses including fever and vasodilation (shock). Endotoxin binds CD14 and TLR4 on macrophages, B cells and other cells to stimulate the release of inflammatory cytokines including IL-1, TNF-alpha, IL-6, and prostaglandins. It is the Lipid A portion of LPS that is responsible for the actual endotoxin activity. Note that LPS is found on the membrane and is therefore not secreted.. Superantigen: specifically activate T cells and trigger life-threatening autoimmune-like responses due to the release of large amounts of IL-1 and IL-2. The activated T cells can also die. Superantigens include toxic shock syndrome (TSS) toxin of S. aureus, staphylococcal enterotoxins, and erythrogenic toxin A or C of S. pyogenes.