Chapter 15 Microbial Mechanisms of Pathogenicity 2013 Pearson

Mechanisms of Pathogenicity § Pathogenicity: the ability to cause disease § Virulence: the extent of pathogenicity § Higher- greater ability to overcome host’s defenses and cause disease § Lower- less ability to overcome host’s defenses and cause disease © 2013 Pearson Education, Inc.

Portals of Entry § § Mucous membranes Skin Parenteral route Preferred portal of entry

Portals of Entry § Mucous Membranes § Respiratory Tract. Streptococcus pneumoniae, Mycobacterium tuberculosis, Influenza virus § Gastrointestinal Tract. Salmonella sp. , Vibrio cholerae § Genitourinary Tract. Neisseria gonorrhoeae, Treponema pallidum, HIV © 2013 Pearson Education, Inc. § Skin or Parenteral § Clostridium perfringens, Clostridium tetani, Hepatitis B virus

Numbers of Invading Microbes § The higher the number of invading microbes the more likely they are to cause disease § ID 50: infectious dose for 50% of the test population § LD 50: lethal dose (of a toxin) for 50% of the test population © 2013 Pearson Education, Inc.

Bacillus anthracis Portal of Entry Skin ID 50 10– 50 endospores Inhalation 10, 000–

Adherence § Adhesins/ligands bind to receptors on host cells § Glycocalyx: Streptococcus mutans §

Figure 15. 1 a Adherence. Adhesin (ligand) Pathogen Host cell surface Receptor Surface molecules on a pathogen, called adhesins or ligands, bind specifically to complementary surface receptors on cells of certain host tissues. © 2013 Pearson Education, Inc.

Figure 15. 1 b-c Adherence. E. coli bacteria (yellow-green) on human urinary bladder cells

HOW BACTERIAL PATHOGENS PENETRATE HOST DEFENSES © 2013 Pearson Education, Inc.

Capsules § Virulence factor § Prevent phagocytosis § Streptococcus pneumoniae § Haemophilus influenzae § Bacillus anthracis § Exception: If body produces antibodies against the capsule, they attach to the capsule and allow the phagocyte to destroy them. © 2013 Pearson Education, Inc.

Enzymes § All are virulence factors. Coagulase: coagulates fibrinogen Kinases: digest fibrin clots Hyaluronidase: hydrolyzes hyaluronic acid Collagenase: hydrolyzes collagen Ig. A proteases: destroy Ig. A antibodies © 2013 Pearson Education, Inc.

Chapter 15, unnumbered figure A, p. 434. Blocked coronary artery © 2013 Pearson Education,

Chapter 15, unnumbered figure B, p. 434. © 2013 Pearson Education, Inc. Necrotizing fasciitis

Antigenic Variation § Organisms change their surface antigens. § Host’s immune system makes specific antibody for specific antigen. Once the antigen changes the antibody in no longer good. © 2013 Pearson Education, Inc.

Penetration into Cytoskeleton § Can manipulate the plasma membrane enough that they are allowed

Figure 15. 2 Salmonella entering intestinal epithelial cells as a result of ruffling. Ruffling

Direct Damage § Disrupt host cell function § Produce waste products § Toxins ©

The Production of Toxins § § § Toxin: substance that contributes to pathogenicity Toxigenicity: ability to produce a toxin Toxemia: presence of toxin in the host’s blood Toxoid: inactivated toxin used in a vaccine Antitoxin: antibodies against a specific toxin © 2013 Pearson Education, Inc.

Figure 15. 4 Mechanisms of Exotoxins and Endotoxins. exotoxins endotoxins Exotoxins are proteins produced inside pathogenic bacteria, most commonly grampositive bacteria, as part of their growth and metabolism. The exotoxins are then secreted into the surrounding medium during log phase. Endotoxins are the lipid portions of lipopolysaccharides (LPS) that are part of the outer membrane of the cell wall of gramnegative bacteria (lipid A; see Figure 4. 13 c). The endotoxins are liberated when the bacteria die and the cell wall breaks apart. Cell wall Exotoxin: toxic substances released outside the cell Clostridium botulinum, an example of a grampositive bacterium that produces exotoxins Salmonella typhimurium, an example of a gramnegative bacterium that produces endotoxins Endotoxins: toxins composed of lipids that are part of the cell membrane © 2013 Pearson Education, Inc.

Exotoxins § Specific for a structure or function in host cell § Will have

Exotoxin Source Relation to microbe Chemistry Mostly gram-positive By-products of growing cell Protein Fever?

Membrane-Disrupting Toxins § Lyse host’s cells by § Making protein channels in the plasma membrane – Leukocidins – Hemolysins – Streptolysins § Disrupting phospholipid bilayer © 2013 Pearson Education, Inc.

Superantigens § Cause an intense immune response due to release of cytokines from host

Endotoxins Source Relation to Microbe Chemistry Gram-negative Outer membrane Lipid A Fever? Yes Neutralized by Antitoxin? No LD 50 Relatively large § Not a specific target so the symptoms are GENERAL. © 2013 Pearson Education, Inc.

Figure 15. 6 Endotoxins and the pyrogenic response. Macrophage Nucleus Endotoxin Hypothalamus of brain Prostaglandin Cytokines Fever Blood vessel Vacuole Bacterium 1 A macrophage ingests a gram-negative bacterium. © 2013 Pearson Education, Inc. 2 The bacterium is degraded in a vacuole, releasing endotoxins that induce the macrophage to produce cytokines IL-1 and TNF-. 3 4 The cytokines are released into the bloodstream by the macrophages, through which they travel to the hypothalamus of the brain. Pituitary gland The cytokines induce the hypothalamus to produce prostaglandins, which reset the body’s “thermostat” to a higher temperature, producing fever.

Cytopathic Effects of Viruses- visible effect of viruses on host cells § Destruction of intracellular contents § Inclusion bodies § Several cells join together to form one GIANT multinucleated cell (syncytium). § Interferons- made by host’s cell in response to viral invasion. Protects neighboring uninfected cells from viral infection. § Change antigenic determinants of host cell causing host’s immune cells to attack their own cell. § Chromosomal damage § No contact inhibition Cancer © 2013 Pearson Education, Inc.

Figure 15. 7 Some cytopathic effects of viruses. Inclusion body Cytoplasmic mass Nuclei ©

Figure 15. 8 Transformed cells in culture. © 2013 Pearson Education, Inc.

Pathogenic Properties of Fungi § Fungal waste products may cause symptoms § Chronic infections provoke an allergic response § Proteases- allow attachment § Candida § Capsule prevents phagocytosis § Cryptococcus § Aflatoxin- toxin with carcinogenic effects § Aspergillus © 2013 Pearson Education, Inc.

Pathogenic Properties of Protozoa § Protozoan waste products may cause symptoms § Avoid host

Pathogenic Properties of Helminths § Use host tissue § Presence of parasite interferes with

Pathogenic Properties of Algae § Paralytic shellfish poisoning § Dinoflagellates © 2013 Pearson Education,

Figure 27. 13 A red tide. © 2013 Pearson Education, Inc.

Portals of Exit § Respiratory tract § Coughing and sneezing § Gastrointestinal tract § Feces and saliva § Genitourinary tract § Urine and vaginal secretions § Skin § Blood § Arthropods that bite; needles or syringes © 2013 Pearson Education, Inc.

Figure 15. 9 Microbial Mechanisms of Pathogenicity. When the balance between host and microbe is tipped in favor of the microbe, an infection or disease results. Learning these mechanisms of microbial pathogenicity is fundamental to understanding how pathogens are able to overcome the host’s defenses. H 1 N 1 flu virus portals of entry Mucous membranes • Respiratory tract • Gastrointestinal tract • Genitourinary tract • Conjunctiva Skin Parenteral route Number of invading microbes penetration or evasion of host defenses Capsules Cell wall components Enzymes Antigenic variation Invasins Intracellular growth Adherence Mycobacterium intracellulare Clostridium tetani Micrographs are not shown to scale. © 2013 Pearson Education, Inc. damage to host cells Siderophores Direct damage Toxins • Exotoxins • Endotoxins Lysogenic conversion Cytopathic effects portals of exit Generally the same as the portals of entry for a given microbe: • Mucous membranes • Skin • Parenteral route