Presentation on theme: "Bacterial Pathogenesis"— Presentation transcript:
1Bacterial Pathogenesis The plague doctor in clothing worn to protect from contagion, circa We are haunted by images of the horrors of disease and death.Very short introduction to Bacteria: worth to see楊倍昌
2Learning ObjectivesAfter reading this section, students will be able to...Explain how to identify a disease pathogen.Describe the modes of infectious disease transmission.Describe how bacteria damage host cells.Explain the mechanisms used by bacteria to evade host defense system.
3共存共生+ Trichonympha(protozoan)Commensalism and symbiosis are presented as part of a continuum, distinguished by the identification of specific benefits derived by one or both members of a host-bacterial partnership.
4Most human infections are caused by opportunistic pathogen. The function of commensal microbe.Probiotics are defined as live cultures of micro-organisms administered orally and acting beneficially on host health.H. Tlaskalov´a-Hogenov´a et al. 2004,Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Letters 93 97–108.
5Death per 100,000, 1952 versus 2007 Some facts (WHO 2008) Gastritis, enteritis, and colitisPneumonia 134.5Tuberculosis, all formsHeart diseaseVascular lesions affecting central nervous systemCause of perinatal mortalityNephritis and nephrosisMalignant neoplamsBronchitisMalariaMalignant neoplasms:Heart diseasesCerebrovascular diseasesDiabetes mellitusAccidentsPneumoniaChronic liver disease and cirrhosisNephritis, nephrotic syndrome, and nephrosisSuicideHypertensive disease
62001 Some facts low- and middle-income countries: Heart disease Stroke Lower respiratory infectionsHIV/AIDSFetus/newborn (perinatal) conditionsChronic obstructive pulmonary disease (COPD)DiarrheaTuberculosisMalariaRoad traffic accidentshigh-income countries:Heart diseaseStrokeLung cancerLower respiratory infectionsChronic obstructive pulmonary disease (COPD)Colon and rectum cancersAlzheimer's diseaseType 2 diabetesBreast cancerStomach cancer
7Innocent or Murder? Who is to be blamed? Not decided. Until… Robert Koch, ,GermanyKoch’s postulates:1. Suspected pathogen must be present2. Pathogen must be isolated and grown in pure culture3. Cultured pathogen must cause the disease4. Same pathogen must be re-isolated from the subject
8Human and microbes Normal flora (beneficial or ignored): GI track, skin, upper respiratory trackVirulent bacteria (actively cause disease): pathogenic islandsOpportunistic bacteria (when host with underline problem):Pseudomonas aeruginosa: cystic fibrosis/ burnTB, Kaposi’s sarcoma (herpesvirus): AIDS
9How Microbs Cause Disease: http://www.youtube.com/watch?v=fNaAisFiPdU Why we do not get ill?(i) the entire invading population is killed by phagocytic cells, such as neutrophils, or circulating bacteriocidal compounds, such as complement, (ii) the density of bacteria traversing the integument is collectively too low to condition the tissue to allow their population to grow, or (iii) the mutations or phase shifts required to get across the mucosa or survive in the blood do not occur.It is complex and strong stochasticHow Microbs Cause Disease:It takes about 1 hr 30 min.
10Bacterial pathogenesis Infection/entryVirulence factorsPathogenesisEscape of immune surveillance
14Where to find the pathogen? Extracellular versus Intracellular ParasitismExtracellular parasitesdestroyed when phagocytosed.damaging tissues as they remain outside cells.inducing the production of opsonizing antibodies, they usually produce acute diseases of relatively short duration.Intracellular parasitescan multiply within phagocytes.frequently cause chronic disease.
18Infection cycle of Listeria monocytogenes. The bacteria mediate their own internalisation into the cell (1). Cellular vacuoles are then lysed by the pore forming toxin listeriolysin O and phospholipase C (2). Once in the cytoplasm the bacteria multiply (5) and rapidly move around the cell by polar polymerisation of host actin: comet-like structure (3). On collision with the cell membrane the bacterium forces its way into the neighboring cell where it lyses the double membrane compartment and the cycle is complete (4)
19Barrier systems Host cell membrane Taken up by phagocyte and resist killingInhibitorymoleculeMycobacteriumProductionOf antibodyDegradeantibodyIgA proteaseStreptococcusAntimicrobiacell-mediatedresponseActivate T cellsnon-specificallyandProductivelySuperantigenStaphylococcusAntimicrobialimmuneVary presentingmicrobial antigenSwitch onproduction ofdifferentantigensBorreliaGeneticrecombination
20Virulence factorsFactors enhance the ability of bacteria to cause diseaseAn example of Pseudomonas aeruginosaAdhesins: attachmentAlginate production: mucoid layerExotoxin A: inhibits host protein synthesisExoenzyme S: interferes with phagocytic killingElastolytic activity: degrades elastinPhospholipase C: damages tissuePyocyanin: damages tissue by ROSAntibiotic resistance: complicates therapy
21Pathogenic action of bacteria Tissue destruction: flesh-eating bacteria: Necrotizing fasciitisObstruction: Cytic fibrosisToxins: bacterial components that directly harm tissue or trigger disease symptomsEndotoxin: lipopolysaccharidesExotoxin: A-B toxinsImmunopathogenesisExcess immune responsesAutoimmunity
22Endotoxins: heat stable IL-6 induced in monocytes exposed to LPS and PM extracts from indoor and outdoor air. Cytokines were measured after exposure of monocytes to particle extracts for six hours.
28Botulinum neutotoxin type B 肉毒素 Clostridium botulinum causes Botulism is a severe type of food poisoning caused by the ingestion of foods containing the neurotoxin formed during growth of the bacteria.can be destroyed if heated to 80ºC for at least 10 minutes.weakness and vertigo, followed by double vision, difficulty in speaking, swallowing and breathing, muscle weakness, abdominal distention, and constipation. Paralysis and death may follow.
29Toxins: affect on nerve-muscle transmission Ästhetik-Forum BerlinBlock the release of ACH
30Tetanus 破傷風 Tetanus toxin: Patient number in Canada After antitoxin vaccine
31Toxins: affect on nerve-muscle transmission The x-ray crystal structure for the tetanus toxin showing how the amino acid chain is folded.
32Aberrant cytokines, cell death SuperantigensPolyclonal T cell activationAntigen/MHC-1Aberrant cytokines, cell deathSpecific T cell activationAnti-microbes immunity
33Known and suspected association of superantigens with human disease (1) Acute diseasesFood poisoning: SEsStaph TSSMenstrual: TSST-1Nonmenstrual: SEB, SEC, TSST-1StrepTSS:SPe’sSudden infant death syndrome: SEs?, SPe,s
34Known and suspected association of superantigens with human disease (2) Autoimmune diseasesRheumatic fever, rheumatic hart disease: M proteins, SPe’s?Kawasaki disease: TSST-1?, SPe’s?Lyme diseaseReumatoid arthritisMultiple sclerosisSjögren’s syndrome:
35EVASION STRATEGIES (1) Defence Microbial strategy Mechanism Example Wash-outBind to cellAdhesinsNeisseriaInhibit ciliaryactivityCiliotoxic/CiliostaticmoleculeBordetellaStreptococcusIngestionandkilling byphagocyteDisruptChemotaxiscytotoxicLeucocidinsStaphylococcusInhibitphagocytosisCapsuleInhibit lysosomalfusion InhibitoryMycobacteriumMultiplyUnknownListeria
36EVASION STRATEGIES (2) Defence Microbial strategy Mechanism Example Restrict Fe- Lactoferrin TransferrinCompeteSiderophoreMycobacterium EscherichiaActivate complementInterfere with alternative pathwayFully sialylated surfaceNeisseriaInactivateElastasePseudomonasAntigen projects beyond surfaceActivation occurs at the wrong siteGram-negativesInterfere with complement- mediated phagocytosis C3b receptor competition, microbe and phagocyteStreptococcus
37Key TakeawaysMost human infections are caused by opportunistic pathogen.Koch’s postulate is the key in pathogen identification that include: 1. Suspected pathogen must be present, 2. Pathogen must be isolated and grown in pure culture, 3. Cultured pathogen must cause the disease, 4. Same pathogen must be re-isolated from the subject.Three modes of disease transmission: Contact, Vehicle, VectorVirulence factors: factors enhance the ability of bacteria to cause disease.Pathogenic actions: Tissue destruction, Obstruction, Toxins, Immunopathogenesis.