Presentation on theme: "Bacterial Pathogenesis"— Presentation transcript:
1 Bacterial 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
2 Learning 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.
4 Most 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.
5 Death 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
6 2001 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
7 Innocent 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
8 Human 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
9 How 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.
10 Bacterial pathogenesis Infection/entryVirulence factorsPathogenesisEscape of immune surveillance
14 Where 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.
18 Infection 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)
19 Barrier systems Host cell membrane Taken up by phagocyte and resist killingInhibitorymoleculeMycobacteriumProductionOf antibodyDegradeantibodyIgA proteaseStreptococcusAntimicrobiacell-mediatedresponseActivate T cellsnon-specificallyandProductivelySuperantigenStaphylococcusAntimicrobialimmuneVary presentingmicrobial antigenSwitch onproduction ofdifferentantigensBorreliaGeneticrecombination
20 Virulence 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
21 Pathogenic 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
22 Endotoxins: 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.
28 Botulinum 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.
29 Toxins: affect on nerve-muscle transmission Ästhetik-Forum BerlinBlock the release of ACH
30 Tetanus 破傷風 Tetanus toxin: Patient number in Canada After antitoxin vaccine
31 Toxins: affect on nerve-muscle transmission The x-ray crystal structure for the tetanus toxin showing how the amino acid chain is folded.
32 Aberrant cytokines, cell death SuperantigensPolyclonal T cell activationAntigen/MHC-1Aberrant cytokines, cell deathSpecific T cell activationAnti-microbes immunity
33 Known 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
34 Known 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:
35 EVASION STRATEGIES (1) Defence Microbial strategy Mechanism Example Wash-outBind to cellAdhesinsNeisseriaInhibit ciliaryactivityCiliotoxic/CiliostaticmoleculeBordetellaStreptococcusIngestionandkilling byphagocyteDisruptChemotaxiscytotoxicLeucocidinsStaphylococcusInhibitphagocytosisCapsuleInhibit lysosomalfusion InhibitoryMycobacteriumMultiplyUnknownListeria
36 EVASION 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
37 Key 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.