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MICROBIOLOGY

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MICROBIOLOGY

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    1. MICROBIOLOGY Reenam Khan - 2nd year medic Nasif Mahmood - 2nd year medic

    2. Whats a virus? 20-240nm Obligate intracellular parasites Nucleic acid + protein

    3. The steps in viruses causing disease Binding Virus proteins bind receptors Penetration enveloped ? fusion at cell surface non-enveloped ? genome/core passes through Eclipse phase Virus proteins expressed Nucleic acids replicated Assembly Release (cell lysis or budding)

    4. Virus Replication- the one-step growth curve

    5. An example- influenza Helical nucleocapsid 13.6kb RNA Ss ve 8 segments enveloped

    6. An example- influenza

    7. Why do new endemics occur? Antigenic Shift - radical change of surface proteins Antigenic Drift - point mutations? small changes in surface proteins

    8. HIV (retrovirus, subgroup lentivirus) 120nm, enveloped 10kb Ss RNA genome +ve Reverse transcription?dsDNA? integration into host DNA. Expression controlled by differential splicing. Regulatory proteins e.g. tat and rev.

    9. HIV structure

    10. HIV (retrovirus, subgroup lentivirus) Transmission- blood products, sexual, mother?baby Gp120 binds CD4 + co-receptor (CCR5 or CXCR4) ? homozygotes for CCR5 mutation are resistant AIDS: T-cell levels drop, unrestricted virus replication, immunodeficiency

    11. HIV drugs Chain terminators e.g. retrovir Protease inhibitors e.g. ritonavir transription, translation, post-translational modification? protein Drug combinations (HAART) (resistance to single drugs develops)

    12. How do chain terminators work?

    13. Preventing viral disease: Passive ? Ig ? maternal antibodies Live (a) Attenuated form of virulent organism (b) Immunologically related organism (c) Virulent organism Dead ? Antigen preparation has infectivity and toxicity inactivated Genetically engineered subunit vaccines/ live organisms ? identify and express genes encoding antigens from protein/virus

    14. Gram Staining: Stain bacteria with violet dye and iodine Rinse in alcohol Stain with red dye

    16. Fungi Eukaryotes E.g. live on bread, release enzymes ? stuff digested outside ? products reabsorbed by diffusion ? spores released for reproduction

    17. Targeting bacteria

    18. Types of fungal infection Allergies (to fungal products) Mycoses (ingestion of fungi and their products) Mycoses (superficial, subcutaenous, systemic)

    19. Fungal cell wall Main distinction between mammalian & fungal cells Main target of antifungal therapy

    20. Antifungal drugs: Must target structures not in humans so not to damage host! Fungi have: ergosterol instead of cholesterol: - synthesis inhibited by azoles e.g. Triazoles (fluconazole) - interaction with ergosterol by polyenes e.g. amphotericin B (b) cell wall made of chitin echinocandins (C) DNA synthesis. Ability to selectively activate some compounds e.g flucytosine

    21. Pathogens: An infecting agent capable of causing disease Whats the difference between a true pathogen and an opportunistic pathogen?

    22. Bacterial Structures:

    23. Antibacterial Drugs Antibiotic = metabolic product of fungi, actinomycetes or bacteria that kills or inhibits the growth of other micro-organisms Antimicrobial = Derived from natural substances which have been chemically modified to improve their activity

    24. Mechanisms of Antibiotic Action

    25. Antibiotic Concepts Whats the difference between a broad spectrum and narrow spectrum antibiotic? Antibiotics can synergise or antagonise each others effects when used together. What does this mean? Whats the difference between a bacteriostatic and bacteriocidal antibiotic?

    26. Antibacterial Resistance When micro-organisms: Produce enzymes that attach to a key bond ?inactivate the antibiotic Change permeability to the antibiotic: alter cell wall or pumping the antibiotic out of the cell Altered structural target Altered metabolic pathway

    27. How does resistance occur? Innate: lack suitable target or impermeable to the agent. Acquired: Mutations? altered target May be acquired by jumping genes (transposons) which can be integrated into either the chromosome or plasmid. a) Cell to cell contact Conjugation b) Transfer by bacteriapharges Transduction c) Transfer of free DNA Transformation *** Therefore use should be limited e.g. not used in animal husbandry ***

    28. Horizontal gene transfer

    29. Pathogenicity islands Result from horizontal gene transfer Differentiate pathogens from their relatives Characteristics e.g. different G/C content from genome average

    30. Techniques for getting past our immune defences

    31. Vaccination

    32. Virulence This refers to the degree of damage and depends on: Tropism Replicate (through nutrient acquisition) Immune invasion Inflict damage e.g using toxins Disseminate

    33. Cholera toxin Toxin co-regulated pilus A1 subunit of toxin ribosylates g-proteins? more GTP? adenyl cyclase stimulation Ion channels stay open Na+, Cl- and H2O loss? profuse, watery diarrhoea

    34. Clostridial Disease Two types of toxins- botulinium and tetani They block exocytosis of neurotransmitter In botulinium: block excitatory transmission? floppy paralysis In tetani: block inhibitory transmission? flaccid paralysis

    35. How does the clostridium toxin exert its effect?

    36. Malaria Cycle

    37. Malaria cycle: terminology Female Anopheles mosquito Liver (Ex-erythrocytic) Sporozoites Schizont Merozoites Hypnozoite Blood (Erythrocytic) Ring Trophozoite Schizont Merozoites Gametocytes Gametes Macro (female) Micro (male)

    38. Quiz time! TRUE or FALSE MCQs Confidence marking: correct incorrect 3 +6 -3 2 +2 -1 1 +1 0

    39. True or False? Eukaryotes have mitochondria

    59. Thank You!

    60. Reminders Membership Next tutorial - send any feedback for the tutorial to nj104@ic.ac.uk or bh04@ic.ac.uk The lecture slides will go online, check the website: http://www.union.ic.ac.uk/medic/muslim/ Any help from us? Please email rk206@ic.ac.uk or mnm04@ic.ac.uk

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