Presentation on theme: "Bacterial Pathogenesis 楊倍昌 1 The plague doctor in clothing worn to protect from contagion, circa 1656. We are haunted by images of the horrors of disease."— Presentation transcript:
Bacterial Pathogenesis 楊倍昌 1 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
Learning Objectives After 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. 2
3 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. 共存 共生 + Trichonympha (protozoan)
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.
Malignant neoplasms: 56.7 Heart diseases 56.2 Cerebrovascular diseases 44.6 Diabetes mellitus 31.1 Accidents 25.7 Pneumonia 22.5 Chronic liver disease and cirrhosis 22.2 Nephritis, nephrotic syndrome, and nephrosis 17.2 Suicide 8.6 Hypertensive disease Gastritis, enteritis, and colitis 135 Pneumonia Tuberculosis, all forms 91.6 Heart disease 49.0 Vascular lesions affecting central nervous system 48.8 Cause of perinatal mortality 44.1 Nephritis and nephrosis 36.3 Malignant neoplams 30.7 Bronchitis 28.1 Malaria 27.5 Death per 100,000, 1952 versus 2007 (WHO 2008) Some facts
6 low- and middle-income countries: 1.Heart disease 2.Stroke 3.Lower respiratory infections 4.HIV/AIDS 5.Fetus/newborn (perinatal) conditions 6.Chronic obstructive pulmonary disease (COPD) 7.Diarrhea 8.Tuberculosis 9.Malaria 10.Road traffic accidents high-income countries: 1.Heart disease 2.Stroke 3.Lung cancer 4.Lower respiratory infections 5.Chronic obstructive pulmonary disease (COPD) 6.Colon and rectum cancers 7.Alzheimer's disease 8.Type 2 diabetes 9.Breast cancer 10.Stomach cancer 2001 Some facts
7 Robert Koch, , Germany Koch’s postulates: 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 Innocent or Murder? Who is to be blamed? Not decided. Until…
8 Human and microbes Normal flora (beneficial or ignored): GI track, skin, upper respiratory track Virulent bacteria (actively cause disease): pathogenic islands Opportunistic bacteria (when host with underline problem): Pseudomonas aeruginosa: cystic fibrosis/ burn TB, Kaposi’s sarcoma (herpesvirus): AIDS
9 (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 stochastic Why we do not get ill? How Microbs Cause Disease: It takes about 1 hr 30 min.
14 Where to find the pathogen? Extracellular versus Intracellular Parasitism Extracellular parasites destroyed 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 parasites can multiply within phagocytes. frequently cause chronic disease.
18 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) Infection cycle of Listeria monocytogenes.
19 Barrier systems Host cell membrane Taken up by phagocyte and resist killing Inhibitory molecule Mycobacterium Production Of antibody Degrade antibody IgA proteaseStreptococcus Antimicrobia cell-mediated response Activate T cells non-specifically and Productively SuperantigenStaphylococcus Antimicrobial immune response Vary presenting microbial antigen Switch on production of different antigens Borrelia Genetic recombination Streptococcus
20 Virulence factors Factors enhance the ability of bacteria to cause disease An example of Pseudomonas aeruginosa Adhesins: attachment Alginate production: mucoid layer Exotoxin A: inhibits host protein synthesis Exoenzyme S: interferes with phagocytic killing Elastolytic activity: degrades elastin Phospholipase C: damages tissue Pyocyanin: damages tissue by ROS Antibiotic resistance: complicates therapy
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.
25 Toxins: Inhibition of protein synthesis Corynebacterium diphtheriae Beta-phage: lysogenic Subunit A
26 Development of vaccine for toxins Diphtheria antitoxin 1901 Nobel prize
27 Toxins: cause hyperactivation Vibrio cholerae
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 Berlin Block the release of ACH
30 Tetanus 破傷風 Tetanus toxin: Patient number in Canada After antitoxin vaccine
31 The x-ray crystal structure for the tetanus toxin showing how the amino acid chain is folded. Toxins: affect on nerve-muscle transmission
32 Superantigens Polyclonal T cell activation Aberrant cytokines, cell death Antigen/ MHC-1 Specific T cell activation Anti-microbes immunity
33 Known and suspected association of superantigens with human disease (1) Acute diseases Food poisoning: SEs Staph TSS Menstrual: TSST-1 Nonmenstrual: SEB, SEC, TSST-1 StrepTSS:SPe’s Sudden infant death syndrome: SEs?, SPe,s
34 Known and suspected association of superantigens with human disease (2) Autoimmune diseases Rheumatic fever, rheumatic hart disease: M proteins, SPe’s? Kawasaki disease: TSST-1?, SPe’s? Lyme disease Reumatoid arthritis Multiple sclerosis Sjögren’s syndrome:
36 Defence Microbial strategy MechanismExample Restrict Fe- Lactoferrin Transferrin CompeteSiderophoreMycobacterium Escherichia Activate complement Interfere with alternative pathway Fully sialylated surface Neisseria InactivateElastasePseudomonas Antigen projects beyond surface Activation occurs at the wrong site Gram-negatives Interfere with complement- mediated phagocytosis C3b receptor competition, microbe and phagocyte Streptococcus EVASION STRATEGIES (2)
Key Takeaways Most 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, Vector Virulence factors: factors enhance the ability of bacteria to cause disease. Pathogenic actions: Tissue destruction, Obstruction, Toxins, Immunopathogenesis. 37