Presentation on theme: "Microbial Mechanisms of Pathogenicity"— Presentation transcript:
1 Microbial Mechanisms of Pathogenicity Chapter 15Microbial Mechanisms of Pathogenicity
2 Microbial Mechanisms of Pathogenicity Pathogenicity The ability to cause diseaseVirulence The extent of pathogenicityMany properties that determine a microbe’s pathogenicity or virulence are unclear or unknownBut, when a microbe overpowers the hosts defenses, disease results!They need to gain entry, adhere, penetrate and cause damage to cause disease.
3 Disease: Pathogens may cause damage to host Direct damage in the immediate vicinityGrow and multiply and clog cells and passagewaysFar removed from site of invasion by toxinsToxins spread through blood and lymphBy hypersensitivityThe host’s reaction may cause the damage
4 Portals of Entry Entry of a Microbe Need to adhere, penetrate, and then cause damageGain access via portal of entry and may a have preferred portal of entry - Streptococcus pneumoniae via GI tract? Small pox via vein?Portals of Entry:Mucous membranesRespiratoryGIUrogenitalconjunctivaSkinTough so rare - Necator americanus - hookwormParenteral routePuncture or injection
5 Mucous Membranes: Respiratory Respiratory Tractmicrobes inhaled into mouth or nose in droplets of moisture or dust particlesEasiest and most frequently traveled portal of entryCommon coldFluTuberculosisWhooping coughPneumoniaMeaslesStrep ThroatDiphtheria
6 Mucous membranes: G.I. Tract SalmonellosisSalmonella sp.ShigellosisShigella sp.CholeraVibrio choloreaUlcersHelicobacter pyloriBotulismClostridium botulinumFecal - Oral DiseasesThese pathogens enter the G.I. Tract at one end and exit at the other end.Spread by contaminated hands & fingers or contaminated food & waterPoor personal hygiene.
7 Mucous Membranes of the Genitourinary System - STD’s GonorrheaNeisseria gonorrhoeaeSyphilisTreponema pallidumChlamydiaChlamydia trachomatisHIVHerpes Simplex II
8 Mucous Membranes: Conjunctiva mucous membranes that cover the eyeball and lines the eyelidTrachomaChlamydia trachomatis
9 2nd Portal of Entry: Skin Skin - the largest organ of the body. When unbroken is an effective barrier for most microorganisms.Some microbes can gain entrance thru openings in the skin: hair follicles and sweat glands
10 3rd Portal of Entry: Parenteral Microorganisms are deposited into the tissues below the skin or mucous membranesPuncturesinjectionsbitesscratchessurgerysplitting of skin due to swelling or dryness
11 Preferred Portal of Entry Just because a pathogen enters your body it does not mean it’s going to cause disease.pathogens - preferred portal of entrySmall pox via variolationStreptococcus pneumoniaeif inhaled can cause pneumoniaif enters the G.I. Tract, no diseaseSalmonella typhiif enters the G.I. Tract can cause Typhoid Feverif on skin, no disease
12 Numbers of Invading Microbes ID50: Infectious dose for 50% of the test populationLD50: Lethal dose (of a toxin) for 50% of the test populationExample: ID50 for Vibrio cholerea cells (100,000,000 cells)ID50 for Inhalation Anthrax - 5,000 to 10,000 spores ????
13 ID50 and LD50 for Bacillus anthracis Portal of entryID50Skin??? endosporesInhalation10,000-20,000 endosporesIngestion250,000-1,000,000 endospores
14 Key traits to a pathogen The ability to:1. AdherenceTo host surfaces and not be washed off2. Avoid phagocytosisPrevent host defenses from destroying3. PenetrateGet into host and spread4. Produce EnzymesSpread, prevent host defenses and cause damage at or near site of infection5. Produce ToxinsCause damage at distant site
15 AdherenceAdhesions/ligands bind to receptors on host cells so won’t get flushed off.Mechanisms to adhere and avoid host defenses:Glycocalyx Streptococcus mutans Dextran (plaque)Waxes MycobacteriaFimbriae Escherichia coliM protein Streptococcus pyogenesTapered end w/ hooks Treponema pallidum
16 Capsules Prevent phagocytosis and help with attachment (adherence) Streptococcus pneumoniaeKlebsiella pneumoniaeHaemophilus influenzaeBacillus anthracisStreptococcus mutansYersinia pestis
17 Enzymes to help penetration Many pathogens secrete enzymes that contribute to their pathogenicity:Increase virulence by use of enzymesAnd avoid phagocytosisCoagulase Coagulate blood - wall off from host make boilKinases Digest fibrin clot - allow spreading streptokinase and staphylolinaseHyaluronidase Hydrolyses hyaluronic acid connective tissueCollagenase Hydrolyzes collagenIgA proteases Destroy IgA antibodiesHemolysins lyse RBC’s
18 Hemolysins Alpha Hemolytic Streptococci Beta Hemolytic Streptococci secrete hemolysins that cause the incomplete lysis or RBC’sBeta Hemolytic Streptococci- secrete hemolysins that cause the complete lysis of RBC’s
19 Leukocidins Enzymes that attack certain types of WBC’s 1. Kills WBC’s which prevents phagocytosis2. Releases & ruptures lysosomeslysosomes - contain powerful hydrolytic enzymes which then cause more tissue damage
20 Enzymes: Necrotizing Factor “Flesh Eating Bacteria”Necrotizing fasciitiscauses death (necrosis) to tissue cells
21 Summary of How Bacterial Pathogens Penetrate Host Defenses 1. Adherence2. Capsule3. EnzymesleukocidinsHemolysinsCoagulaseKinasesHyaluronidaseCollagenaseNecrotizing Factor
23 Toxins Provide properties to spread and cause damage to the host. Compare endotoxins and exotoxinsEndotoxins from inside the cell. Released upon cell lysis.Exotoxins are secreted out of the cell during cell life.Toxin Substances that contribute to pathogenicityToxigenicity Ability to produce a toxinToxemia Presence of toxin the host's bloodToxoid Inactivated toxin used in a vaccineAntitoxin Antibodies against a specific toxin
24 Exotoxins Mostly seen in Gram (+) Bacteria Most gene that code for exotoxins are located on plasmids or phagesFigure 15.4a
25 Exotoxin Exotoxin Source Mostly Gram + Metabolic product By-products of growing cellChemistryProteinWater solubleFever?NoNeutralized by antitoxinYesLD50Small - Very potent1 mg of Clostridium botulinum toxin can kill 1 million guinea pigs
26 Exotoxins - three types 1. Cytotoxinskill cells2. Neurotoxinsinterfere with normal nerve impulses3. Enterotoxinseffect cells lining the G.I. TractMany toxins have A-B subunit toxins or type III toxinsA - activeCauses change in hostB - bindingFigure 15.5
27 Exotoxins Superantigens or type I toxins Cause an intense immune response due to release of cytokines from host cellsFever, nausea, vomiting, diarrhea, shock, death
28 Exotoxins Cholera enterotoxin Membrane-disrupting toxins or type II toxinsLyse host’s cells by:Making protein channels in the plasma membrane (e.g., leukocidins, hemolysins)Disrupting phospholipid bilayerCholeraenterotoxinVibrio choleraeGram (-) comma shaped rods
29 Exotoxins Exotoxin Lysogenic conversion • Corynebacterium diphtheriae A-B toxin type III. Inhibits protein synthesis.+• Streptococcus pyogenesMembrane-disrupting. Type II Erythrogenic.• Clostridium botulinumA-B toxin. Neurotoxin - flaccid paralysisBotox• C. tetaniA-B toxin. Neurotoxin - prevents CNS inhibition - spastic paralysis• Vibrio choleraeA-B toxin. Enterotoxin. Stimulates cAMP to cause severe diarrhea• Staphylococcus aureusSuperantigen. Type I. Enterotoxin.
30 Botox Botulism Clostridium botulinum Gram (+), anaerobic, spore-forming rod, found in soilworks at the neuromuscular junctionprevents impulse from nerve cell to muscle cellresults in muscle paralysisBotulus – latin word for sausage (first known as sausage disease) C. botulinum does not grow in sausage today mainly due to nitrites added. Infant botulism 250 per yr., most associated with honey due to little microbial flora in G.I.
31 Tetanus (Lock Jaw) Clostridium tetani Gram (+), spore-forming, anaerobic rodneurotoxin acts on nerves, resulting in the inhibition of muscle relaxationTetanospasmin - “spasms” or “Lock Jaw”50 cases a yr. in U.S.1 million per yr. Worldwide50% in newborns – because they dress severed umbilical cord with soil, clay or cow dung Tetanospasmin inhibits the release of acetylcholine by interfering with activity of cholinesterase (enzyme that normally breaks down acetylcholine)
33 Endotoxins Source Gram– Metabolic product Present in LPS of outer membraneChemistryLipidFever?YesNeutralized by antitoxinNoLD50Relatively large
34 Endotoxins - part of the Gram (-) Bacterial cell wall LPS (Lipopolysaccharides)O AntigenLipid AHeat Stable (exotoxins are typically heat liable)Lipid A - Toxin portion of the LPSresponsible for Fever that is associated with many Gram (-) Bacterial infectionsGram (-) cells are “digested” endotoxins are released - feverAntibioticsE. coli (0157:H7)enterotoxin causes a hemolytic inflammation of the intestinesresults in bloody diarrhea
38 Pathogenic Properties of Fungi Fungal waste products may cause symptomsChronic infections provoke an allergic responseTichothecene toxins inhibit protein synthesisFusariumProteasesCandida, TrichophytonCapsule prevents phagocytosisCryptococcusErgot toxinClaviceps
39 Pathogenic Properties of Fungi AflatoxinAspergillus on peanuts?MycotoxinsNeurotoxins: Phalloidin, amanitinAmanita “death angel” - Liver damage
40 Pathogenic Properties of Protozoa Presence of protozoaProtozoan waste products may cause symptomsAvoid host defenses byGrowing in phagocytesAntigenic variation
41 Pathogenic Properties of Helminths Use host tissuePresence of parasite interferes with host functionParasite's metabolic waste can cause symptomsDeath can cause excessive immune reaction leading to more symptoms
42 Pathogenic Properties of Algae Neurotoxins produced by dinoflagellatesSaxitoxinParalytic shellfish poisoning