Bio Microbiology - Spring 2010 Study Guide 21

Transcription

1 Bio Microbiology - Spring 2010 Study Guide 21

2 Factors in Microbial Disease Host Parasite Interactions are Dynamic Evolution effects both Parasite and Host

3 Pathogenic Properties of Bacteria Microorganisms cause disease by two basic mechanisms: 1) invasion of tissue 2) production of toxins. Invasiveness: the ability to invade host tissues. Toxigenicity: the production of toxins.

4 Virulence: the combination of invasiveness and toxigenicity producing the ability to overcome host defenses. Measurement of virulence: LD50 (% dead vs dose). Variability in virulence potential may be genotypic

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6 There are many genes needed to make an an organism Pathogenic. Consider the different types of genes that could be involved in pathogenicity of an organism such as Salmonella. a. Adhesion b. Invasiveness c. Overcoming host defense d. Toxins

7 Virulence factors of Helicobacter 1. Colonisation factors, which allow the bacteria to initially gain access to their host. 2. Persistence factors, which allow the bacteria to remain in the host in some cases for months or years. 3. Disease inducing factors, which over time cause damage to the host tissue and induce pathology. Cytolethal distending toxin (CDT)

8 How can you prove that a gene is involved in Pathogenicity? Knowing the details provides targets for preventing or managing disease

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10 TERMS USED TO DESCRIBE ADHERENCE FACTORS IN HOST-PARASITE INTERACTIONS ADHERENCE FACTOR Adhesin Receptor Lectin Ligand Mucous Fimbriae Common pili Sex pilus Type 1 fimbriae Glycocalyx Capsule Lipopolysaccharide (LPS) Teichoic acids and lipoteichoic acids (LTA)

11 Anti-Adhesins Hope for the post-antibiotic era? Randall T. Irvin & Daisy L. Bautista Nature Biotechnology 17, 20 (1999)

12 Spreading Factors Staphylococcal coagulase Enzymes that Cause Hemolysis and/or Leucolysis Extracellular Digestive Enzymes Toxins With Short-Range Effects Related to Invasion Invasins Invasin Bacteria Involved Activity Hyaluronidase Streptococci, staphylococci and clostridia Degrades hyaluronic of connective tissue Collagenase Clostridium species Dissolves collagen framework of muscles Neuraminidase Vibrio cholerae and Shigella dysenteriae Degrades neuraminic acid of intestinal mucosa Coagulase Staphylococcus aureus Converts fibrinogen to fibrin which causes clotting Kinases Staphylococci and streptococci Converts plasminogen to plasmin which digests fibrin Leukocidin Staphylococcus aureus Disrupts neutrophil membranes and causes discharge of lysosomal granules Streptolysin Streptococcus pyogenes Repels phagocytes and disrupts phagocyte membrane and causes discharge of lysosomal granules Hemolysins Streptococci, staphylococci and clostridia Phospholipases or lecithinases that destroy red blood cells (and other cells) by lysis Lecithinases Clostridium perfringens Destroy lecithin in cell membranes Phospholipases Clostridium perfringens Destroy phospholipids in cell membrane Anthrax EF Bacillus anthracis One component (EF) is an adenylate cyclase which causes increased levels of intracellular cyclic AMP Pertussis AC Bordetella pertussis One toxin component is an adenylate cyclase that acts locally producing an increase in intracellular cyclic AMP

13 Iron transporters

14 Toxins PROPERTY ENDOTOXIN EXOTOXIN CHEMICAL NATURE Lipopolysaccharide(mw = 10kDa) Protein (mw = kDa) RELATIONSHIP TO CELL Part of outer membrane Extracellular, diffusible DENATURED BY BOILING No Usually ANTIGENIC Yes Yes FORM TOXOID No Yes POTENCY Relatively low (>100ug) Relatively high (1 ug) SPECIFICITY Low degree High degree ENZYMATIC ACTIVITY No Usually PYROGENICITY Yes Occasionally

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19 King Cholera dispenses contagion: the London cholera epidemic of By Geroge John Pinwell. Traced to a water pump on Broadwick Street, Soho (near the convivial Blue Post pub) by Dr John Snow, among the most important applications of scientific method to medicine.

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21 Original map by Dr. John Snow showing the clusters of cholera cases in the London epidemic of 1854

22 Spread of Epidemic Cholera - Latin American

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24 Cholera Toxin Action of cholera toxin. A, B (cholera toxin subunits); GM1 (GM1 ganglioside receptor); Gsa (G protein); AC (adenylate cyclase); Gi (G protein); camp (cyclic AMP); CFTR (cystic fibrosis transmembrane conductance regulator).

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27 LAL Milestones 1880 W. H. Lowell first studies coagulation of L. polyphemus blood at Johns Hopkins University Bang discovers that horseshoe crab blood forms clots when bacteria (Vibrio sp.) are present Levin and Bang discover that the blood clotting agent in horseshoe crabs is an amoebocyte Scientists discover that an endotoxin causes blood-clot reaction in horseshoe crabs. The method for preparing LAL from horseshoe crab blood is developed The standard LAL assay is developed FDA replaces the standard rabbit test for endotoxins with the LAL test FDA accepts LAL as a standard test for bacterial endotoxin contamination FDA establishes guidelines for LAL testing of pharmaceuticals and medical devices.

28 Pathogenic cycle of Legionella

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30 Coagulase Positive Staphylococcus Staphylococcus aureus 1. The Carrier State 2. Direct Infection 3. Bloodstream Infections Secondary to Above 4. Toxin Mediated Disease

31 Virulence factors of Staphylococcus aureus No single factor is decisive for virulence. No protective immune response is made. Infections with S. aureus can be acquired again and again.

32 The End