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Plants and Fungi Used to Treat Infectious Disease

Plants and Fungi Used to Treat Infectious Disease. Infectious Disease. World wide, infectious disease is the number one cause of death accounting for approximately one-half of all deaths in tropical countries

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Plants and Fungi Used to Treat Infectious Disease

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  1. Plants and Fungi Used to Treat Infectious Disease

  2. Infectious Disease • World wide, infectious disease is the number one cause of death accounting for approximately one-half of all deaths in tropical countries • Infectious disease mortality rates are actually increasing in developed countries, such as US • Infectious disease underlying cause of death in 8% of deaths occurring in US

  3. Terms • Antimicrobial = a substancewhich destroys or inhibits the growth of microorganisms • Antiseptic = a substance that checks the growth or action of microorganisms especially in or on living tissue • Antibiotic = a substance produced by or derived from a microorganism and able to inhibit or kill another microorganism

  4. Overview • Antibiotics from fungi • Antimalarials from plants • Other antimicrobials from plants

  5. Penicillin • By-product of certain Penicillium species • Inhibits the growth of gram-positive bacteria • Blocks wall synthesis in bacteria and results in death of the bacterial cell by lysis • Surpassed known therapeutic agents by suppressing bacterial growth without being toxic

  6. Discovery of Penicillin • Folk treatments for wounds • 19th Century observations of antibiosis by Penicillium spp • Roberts - 1874 • Tyndall - 1881 • Others • Flemming - 1928

  7. Sir Alexander Fleming

  8. Fleming’s Petri Dish - Penicillium notatum killed the culture of Staphylococcus aureus

  9. Zone of Inhibition • Around the fungal colony is a clear zone where no bacteria are growing • Zone of inhibition due to the diffusion of a substance with antibiotic properties from the fungus

  10. Research continues • In 1939, - Oxford University Howard Florey and Ernst Chain • 1941 first human tests • 1941 research moved to the US • USDA labs in Peoria Illinois • Summer 1943 Penicillium chrysogenum • D-Day 1944 • 1945 Nobel Prize

  11. Start of Synthetics • Soon after World War II, the pharmaceutical industry developed chemically altered versions of the penicillin molecule • Modified penicillins provided for greater stability, broader anti-bacterial activity, and also oral administration which would permit home use of antibiotics

  12. Penicillin Today • Still the most widely used antibiotic • Still the drug of choice to treat many bacterial infections • Scientists have continued to improve the yield of the drug • Present day strains of P. chrysogenum are biochemical mutants that produce 10,000 times more penicillin than Fleming's original isolate

  13. Drawbacks • Resistance - evolution of penicillin-resistantbacteria • Allergies - Penicillin is the most frequent cause of anaphylaxis

  14. Synthesis of Penicillin • Penicillin - one of a family of b-Lactam antibiotics • b-Lactams produced by asexual fungi, some ascomycetes, and several actinomycete bacteria • b-Lactams are synthesized from amino acids valine and cysteine

  15. b Lactam Basic Structure

  16. Penicillins • When penicillin first isolated, it was found to be a mixture of various penicillins • Different R groups attached to the molecule • When large scale production began, it was found that by adding phenylacetic acid to the medium, the penicillin was all one type -penicillin-G

  17. Penicillin-G

  18. Penicillin-G • Still an important antibiotic • Disadvantage has been that it is unstable in acid conditions • Given by injections - otherwise stomach acids would destroy

  19. Penicillin-V • The addition of phenoxyacetic acid to the culture medium gives penicillin-V • This is not as active as penicillin-G, but it is acid stable and can be given by mouth • There are many other naturally occurring penicillins but these are still clinically very important

  20. Penicillin-V phenoxy methyl penicillin

  21. Semi-Synthetic Penicillins • A strain of Penicilliumchrysogenum found that produced large amounts of 6-amino penicillanic acid (6-APA) • 6-APA lacked antibiotic activity but it could be used to add a variety of side chains and create semi-synthetic penicillins • methicillin and ampicillin • Semi-synthetics have made penicillins a more versatile group of antibiotics

  22. R=H 6-APA Ampicillin Methycillin

  23. Mode of Action • b-lactam antibiotics inhibit formation of the bacterial cell wall by blocking cross-linking of the cell wall structure • Bind to PBP – penicillin binding proteins in cell membrane that function as transpeptidases • Inhibit transpeptidases, which catalyze the final cross linking step in the synthesis of the peptidoglycan cell wall • Result: bacterial wall is weakened and cell bursts from osmotic pressure

  24. Resistance due to b-Lactamase

  25. Cephalosporin • In 1948 Giuseppe Brotzu identified a compound produced by Cephalosporium acremonium that was an effective treatment for gram-positive infections as well as some gram-negative ones such as typhoid • Brotzu sent a culture of this fungus to Florey. The team at Oxford once again isolated the active compound which they named cephalosporin • Today a whole class of cephalosporins

  26. Cephalosporin

  27. Clinically Important Antibiotics

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