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Microbial Mechanisms of Pathogenicity

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Presentation on theme: "Microbial Mechanisms of Pathogenicity"— Presentation transcript:

1 Microbial Mechanisms of Pathogenicity

2 LEARNING OBJECTIVES Identify the principal portals of entry and exit.
Using examples, explain how microbes adhere to host cells. Explain how capsules and cell wall components contribute to pathogenicity. Compare the effects of coagulases, kinases, hyaluronidase, and collagenase. Describe the function of siderophores. Provide an example of direct damage, and compare this to toxin production. Contrast the nature and effects of exotoxins and endotoxins. Outline the mechanisms of action of A-B toxins, membrane-disrupting toxins, and superantigens Classify diphtheria toxin, erythrogenic toxin, botulinum toxin, tetanus toxin, Vibrio enterotoxin, and staphylococcal enterotoxin

3 Vocabulary Attachment is step 1: Bacteria use ___________ ___________
Pathogenicity: Ability of a pathogen to cause disease by overcoming the host defenses Virulence: Degree of pathogenicity. Attachment is step 1: Bacteria use ___________ ___________ Viruses use ___________

4 (Preferred) Portals of Entry
Mucous membranes Conjunctiva Respiratory tract: Droplet inhalation of moisture and dust particles. Most common portal of entry. GI tract: food, water, contaminated fingers Genitourinary tract Skin Impenetrable for most microorganisms; can enter through hair follicles and sweat ducts. Parenteral Route Trauma (S. aureus, C. tetani) Arthropods (Y. pestis) Injections

5 Numbers of Invading Microbes
ID50: Infectious dose for 50% of the test population LD50: Lethal dose (of a toxin) for 50% of the test population Bacillus anthracis Portal of Entry ID50 Skin 10–50 endospores Inhalation 10,000–20,000 endospores Ingestion 250,000–1,000,000 endospores Clinical and Epidemiologic Principles of Anthrax at

6 Adherence Adhesins: surface projections on pathogen, mostly made of glycoproteins or lipoproteins. Adhere to complementary receptors on the host cells. Adhesins can be part of: Glycocalyx: e.g.Streptococcus mutans Fimbriae (also pili and flagella): e.g.E. coli Host cell receptors are most commonly sugars (e.g. mannose for E. coli Biofilms provide attachment and resistance to antimicrobial agents.

7 Overcoming Host Defenses
Capsules: inhibition or prevention of _____________ Cell Wall Proteins: e.g. M protein of S. pyogenes Antigenic Variation: Avoidance of IS, e.g. Trypanosoma Neisseria Penetration into the Host Cell Cytoskeleton: Salmonella and E. coli produce invasins, proteins that cause the actin of the host cell’s cytoskeleton to form a basket that carries the bacteria into the cell. ANIMATION Virulence Factors: Hiding from Host Defenses

8 Penetration into the Host Cell Cytoskeleton
Invasins Salmonella alters host actin to enter a host cell Use actin to move from one cell to the next Listeria Fig 15.2

9 Enzymes Coagulase: Blood clot formation. Protection from phagocytosis (virulent S. aureus) Kinase: blood clot dissolve (e.g.: streptokinase) Hyaluronidase: (Spreading factor) Digestion of “intercellular cement”  tissue penetration Collagenase: Collagen hydrolysis IgA protease: IgA destruction

10 Enzymes Used for Penetration

11 How Pathogens Damage Host Cells
Use host’s nutrients; e.g.: Iron Cause direct damage Produce toxins Induce hypersensitivity reaction ANIMATION Virulence Factors: Penetrating Host Tissues ANIMATION Virulence Factors: Enteric Pathogens

12 Toxins Exotoxins: proteins (Gram- and + bacteria can produce)
Endotoxins: Gram- bacteria only. LPS, Lipid A part  released upon cell death. Symptoms due to vigorous inflammation. Massive release  endotoxic shock Foundation Fig 15.4 ANIMATION Virulence Factors: Exotoxins

13 Vocabulary related to Toxin Production
Toxin: Substances that contribute to pathogenicity. Toxigenicity: Ability to produce a toxin. Toxemia: Toxoid: Antitoxin: Antitoxin: Antibodies against a specific toxin.

14 By-products of growing cell
Exotoxins Summary Source: Gram + and Gram - Relation to microbe: By-products of growing cell Chemistry: Protein Fever? No Neutralized by antitoxin? Yes LD50: Small Circulate to site of activity. Affect body before immune response possible. Exotoxins with special action sites: Neuro-, and enterotoxins

15 Toxin Examples Portal of Entry ID50 Botulinum (in mice) 0.03 ng/kg
Shiga toxin 250 ng/kg Staphylococcal enterotoxin 1350 ng/kg Which is the least potent toxin? Botulinum Shiga Staph

16 Type of Exotoxins: A-B Exotoxins
Fig 15.5 Fig 15.5

17 Membrane-Disrupting Toxins
Lyse host’s cells by Making protein channels into the plasma membrane, e.g. S. aureus Disrupting phospholipid bilayer, e.g. C. perfringens Examples: Leukocidin: PMN and M destruction Hemolysin (e.g.: Streptolysin) : RBCs lysis  get at?

18 Superantigens Special type of Exotoxin
Nonspecifically stimulate T-cells. Cause intense immune response due to release of cytokines from host cells. Fever, nausea, vomiting, diarrhea, shock, and death.

19 Representative Examples of Exotoxins
Bacterial Species Exotoxin Lysogeny C. diphtheriae A-B toxin + S. pyogenes Membrane-disrupting erythrogenic toxin C. botulinum A-B toxin; neurotoxin C. tetani V. cholerae A-B toxin; enterotoxin S. aureus Superantigen

20 Endotoxins Bacterial cell death, antibiotics, and antibodies may cause the release of endotoxins. Endotoxins cause fever (by inducing the release of interleukin-1) and shock (because of a TNF-induced decrease in blood pressure). TNF release also allows bacteria to cross BBB. The LAL assay (Limulus amoebocyte lysate) is used to detect endotoxins in drugs and on medical devices. Fig 15.6

21 Endotoxin Summary Source: Gram – Relation to microbe:
Present in LPS of outer membrane Chemistry: Lipid A component of LPS Fever? Yes Neutralized by antitoxin? No LD50: Relatively large

22 Inflammation Following Eye Surgery
Patient did not have an infection The LAL assay of solution used in eye surgery What was the cause of the eye inflammation? What was the source? Clinical Focus, p. 440

23 Pathogenic Properties of Viruses
Evasion of IS by Growing inside cells Rabies virus spikes mimic Ach HIV hides attachment site  CD4 long and slender Visible effects of viral infection = Cytopathic Effects cytocidal (cell death) noncytocidal effects (damage but not death).

24 Pathogenic Properties of Fungi
Fungal waste products may cause symptoms Chronic infections provoke allergic responses Proteases Candida, Trichophyton Capsule prevents phagocytosis Cryptococcus Fungal Toxins Ergot toxin Claviceps purpurea Aflatoxin Aspergillus flavus This month's fungus is a plant parasite, commonly found on grains of rye (as shown here) or sometimes on other grasses such as quackgrass. The fungus infects the flowers when they're young and cause the growths you see. It induces the cells to divide (hyperplasia) and to enlarge (hypertrophy), creating the relatively large brown sclerotia to the left. These sclerotia are hard resting structures that allow the fungus to survive adverse conditions, such as winter and desiccation. In the life cycle of this organism, the sclerotia fall to the ground and overwinter, germinating in the spring to produce a stroma that contains perithecia, which produces spores to. Someday I'll have a good picture of this to put online-- the stroma are fragile and don't photograph well so far. It's really not a devastating parasite to the plant. You might think its main detriment is that is replaces one of the grains of the plant, thus reducing yield. However it also draws nutrients away from the other uninfected grains so that they become stunted, thus reducing yield quite a bit more. But its worst problem is when the sclerotia inadvertently get mixed in with the grains and are incorporated into foods, thus causing a devastating and sometimes deadly syndrome called ergotism in humans and other animals. Ergotism is caused by the chemicals in the fungus called ergot (pronounced AIR-got). Consumption of foods contaminated with ergot and ergot derivatives may cause vomiting, diarrhea, hallucinations, and may lead to gangrene in serious cases. Historically the fungus has been implicated in epidemics causing thousands of fatalities, but due to increased knowledge of this fungus and a more varied modern diet such epidemics no longer occur in humans. However, chronic exposure through consumption of contaminated foods can lead to health complications. However as recently as 1951, in Pont-St. Esprit, a small town in France, there was an outbreak of the disease. First a bit of background-- in Europe it is the custom to buy fresh bread nearly every day. Much more civilized than our American custom of buying bread with preservatives in it that allow it to last several weeks. In this small town there was only one bakery and everyone bought bread from it. Strange things started happening. People developed a burning sensation in their limbs, began to hallucinate that they could fly, did strange things to their dogs with forks and in general acted weirdly. This outbreak is chronicled in a marvelous (but out of print) book called "The day of St Anthony's Fire" by John Grant Fuller. St. Anthony is the patron saint of lost causes (incidentally I went to St. Anthony's church until I was about 18). When all of the other saints have failed, St. Anthony is the one you are supposed to pray to. And St. Anthony's fire was rampant in the town that day. Similar outbreaks probably occurred throughout the world wherever the conditions were right for the growth of Claviceps purpurea. The chemical responsible for the hallucinations is actually LSD! lysergic acid. There was even an outbreak of egotism on the television show "Quincy" starring Jack Klugman, who played a coroner. He was aboard a cruise ship and people were acting very strangely. Quincy finally traced the behavior to contamination of the flour tortillas that had been served aboard ship. I haven't seen this episode for 15 years, but I still remember it because I figured it out before Quincy did!

25 Pathogenic Properties of Protozoa & Helminths
Presence of protozoa Protozoan waste products may cause symptoms Avoid host defenses by Growing in phagocytes Antigenic variation Presence of helminths interferes with host function Helminths metabolic waste can cause symptoms Wuchereria bancrofti

26 Portals of Exit Respiratory tract: Coughing and sneezing
Gastrointestinal tract: Feces and saliva Genitourinary tract: Urine and vaginal secretions Skin Blood: Biting arthropods and needles or syringes

27 Microbial Mechanisms of Pathogenicity - Overview
Foundation Fig 15.9 The End

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