Bacterial Pathogenesis Flashcards
What are intrinsic characteristics of bacteria that contribute to pathogenicity?
Virulence Factors
What is a pathogenicity island?
Large segments of DNA that carry virulence genes acquired by horizontal gene transfer. They are activated by stimulus or quorum sensing.
What are some of the main bacterial virulence factors?
- Adherence
- Enzymes
- Glycocalyx & Biofilms
- Toxins
What are the two ways in which bacteria adhere to hosts or surfaces?
Adhesins & Biofilms
What are the mechanisms for bacterial host evasion?
- Defense against antibodies
- Antigenic masking to block phagocytic recognition
- Other antiphagocytic measures
- Inhibition of chemotaxis
What are adhesins?
Surface projections that bind to receptors on the host cell surface, such as fimbriae and pili. These structures may be part of the glycocalyx (capsule or slime layer).
What functions do adhesins serve?
- Promote attachment and colonization, but not necessarily invasion
- Complete with normal flora for nutrients
- Promote avoidance of host defenses
- Stimulate inflammatory response
What is a biofilm?
An aggregate of microorganisms adhered to each other and resist clearance. They may form on living or non-living surfaces and reduce the efficacy of antibiotics.
What is quorum sensing?
Regulation of gene expression based on signal compounds released by large numbers of nearby cells. These genes promote growth and organism survival.
Describe the process by which a biofilm forms.
Free-floating bacteria attach to a surface. Bacteria begin to college and are held together by exopolsaccharide (EPS). EPS enables the biofilm to develop a complex structure. Alignate is a compound in EPS that inhibits innate immune defenses.
What are the common invasins produced by bacteria to promote spreading and invasion?
- Hyaluronidase
- Collagenase
- Streoptokinase/Stapholykinase
- Neuraminidase
What is the function of the hyaluronidase?
Cleaves hyaluronic acid, which is a component of the epithelial matrix, to cause tissue penetration
What invasin converts inactive plasminogen to plasmin, which digests fibrin and prevents blood clotting?
Streptokinase/Staphylokinase
What is the function of collagenase?
Breaks down collage in connective tissues
What is the function of neuraminidase?
Degrades sialic acid in the epithelial cells of the intestinal mucosa
What are the common degradative enzymes produced by bacteria?
- Lecithinase
- Phospholipase
- Leukocidin/Streptolysin
- Hemolysins
What degrative enzyme lyses phagocytes and their granules?
Leukocidin/Streptolysin
What is the function of phospholipase?
Breaks down phospholipids in the cell membrane
What degradative enzyme destroys lecithin in the cell membrane?
Lecithinase
What is the function of hemolysins?
Lyse erythrocytes
What are bacteria that require invasion of host cells for growth and survival?
Obligate intracellular bacteria
What are facultative intracellular bacteria?
Bacteria that invade the cell as part of pathogenesis, but do not require invasion for survival
How do bacteria defend against host antibodies?
- Produce anti-IgA proteases that cross mucosal tissues
- Antigenic shift
What mechanisms do bacteria utilize to prevent recognition by phagocytes?
- Production of coagulase to convert fibrinogen to fibrin, causing clots
- Bind fibronectin to its surface
- Capsules or slime layers
- Prevent opsonization by complement
What mechanisms do bacteria utilize to avoid phagocytosis?
- Inhibition of phagolysosomal fusion
- Resist lysosomal enzyme activity
- Phagocyte destruction
- Prevention of opsonization
- Complement modulation
What is the mechanism of Staphylococcus aureus protein A to prevent opsonization?
The protein binds the Fc region (body) of the antibody to prevent bonding with the antigen site
What are the three types of exotoxins?
Enterotoxin, neurotoxin, cytotoxin
How do exotoxins differ from endotoxins?
Exotoxins are actively released out while endotoxins are components of the outer leaflet of the outer membrane and released during cell death.
Exotoxins are generally heat liable and very toxic, while endotoxins are heat stable and weakly toxic.
Only G- bacteria produce endotoxins.
Describe the process of receptor-mediated endocytosis of A=B toxins.
The B subunit binds to a receptor on the cell. The A+B structure is internalized in an endosome. The low pH of the endosome separates the A+B subunits. The A subunit is released from the endosome and the B subunit is recycled to the surface.
Describe the process of direct entry of A+B toxins.
The B subunit binds a cell receptor. Binding induces formation of a membrane pore through which the A subunit is transferred.
What are the general main mechanisms of exotoxins?
- Inhibit protein synthesis
- Hyperactivation of cell proteins
- Pore formation in cell membrane
- Interference with nerve transmission
- Non-specific T-cell activation
What toxins act at elongation factor 2 to inhibit protein elongation and ultimately lead to cell death?
- Diphtheria toxin
- Exotoxin A
How do the Shiga Toxin and Shiga-like toxin inhibit protein synthesis?
Inactivate the 60S subunit of ribosomes by cleaving rRNA
What toxin causes hyperactivation of the G protein to produce cAMP, causing loss of Cl- and H2O?
Cholera Toxin
This toxin disrupts the membrane, creating pores that cause hemolysis and tissue damage.
Staphylococcus aureus alpha toxin
What is the mechanism of Clostridium perfringens alpha toxin?
Phospholipase targets cholesterol in the membrane and is responsible for gas gangrene and myoneocrosis.
What is the mechanism of Clostridium tetani tetanospasmin?
The toxin targets nerve-nerve junctions. It binds the axon, cleaves docking patters (SNARES), and prevents release of GABA and glycine. The result is spastic paralysis.
This is the opposite effect of Clostridium botulinum toxin.
What is the mechanism of the Clostridium botulinum toxin?
Acts on neuromuscular junctions. The toxin cleaves docking proteins (SNARES) and prevents release of ACH, resulting in paralysis.
This is the opposite effect of Clostridium tetani tetanospasmin.
What is the mechanism of superantigens?
Non-specifically bind T cells, activating overwhelming cytokines and proinflammatory cytokines. May lead to toxic shock.
What component of the G- cell membrane is responsible for endotoxin toxicity?
Lipid A (part of LPS)
Describe the mechanism by which Lipid A affects the body.
LPS is released when a G- cell dies. Free floating LPS is bound by a LPS binding protein, which then binds a macrophage. The macrophage then releases proinflammatory cytokines. These cytokines then activate the coagulation pathway, result in prostaglandins and leukoreins, and activation of complement pathways. This may result in damage to blood vessels and epithelium, acute respiratory distress, shock, and organ system failure.
How are toxin-mediated diseased diagnosed?
- Identification of toxin-producing bacteria
- Identification of exotoxin in specimen
What treatments are utilized for toxin-mediated diseases?
- Antibiotic treatment
- Passive immunization
- Vaccination with toxoid (inactive form of toxin)
