传染性疾病的抗菌治疗（英文ppt）plantsand fungi used to treat infectious

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 Infectious disease mortality rates are actually increasing in developed countries, such as US Death from infectious disease, ranked 5th in 1981, has become the 3rd leading cause of death in 1992 Infectious disease underlying cause of death in 8% of deaths occurring in US Terms Antimicrobial = a substance which 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 Antibiotics vs Antimicrobials Antibiotics are toxic to microorganisms Produced by fungi and/or bacteria In the natural environment, antibiotics give the producing organism advantages over competing microorganisms for available nutrients and space First antibiotic put into large-scale production was penicillin Antibiotics vs Antimicrobials Antimicrobials produced by a variety of organisms including many plants Plant-based antimicrobials provide protection for the plant against pathogenic bacteria or fungi Plant-based antimicrobials represent a vast untapped source for medicines Plants-based antimicrobials have enormous, but largely untapped, therapeutic potential for treating infectious disease Overview Antibiotics from fungi Antimalarials from plants Other antimicrobials from plants 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 Discovery of Penicillin Infusions of moldy bread, cheese, meat, and soybeans have long history as folk treatment for wounds 19th Century observations of antibiosis by Penicillium spp Roberts - 1874 Tyndall - 1881 others Discovery of Penicillin First discovered in 1928 by British physician Alexander Fleming Accidental discovery of a contaminated bacterial culture Fungus Penicillium notatum killed the culture of Staphylococcus aureus growing in the petri dish Sir Alexander Fleming Flemings Petri Dish 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 Additional work Fleming carried out additional experiments, named it penicillin and published his findings Flemings paper attracted little attention at the time Flemings experiments at purifying penicillin failed It was 11 yrs before research advanced Research at Oxford University In 1939, Howard Florey and Ernst Chain began investigating naturally occurring antibacterial compounds and came across Flemings report on penicillin Within a year, the team at Oxford had chemically analyzed the compound and demonstrated that it could destroy certain types of bacteria in test tubes Progress Continues War in Europe was escalating and Florey and Chain realized the potential for treating war wounds Tests on infected animals were successful 1941 the first human tests were conducted Research was moved to various sites in the United States because of the war Really miraculous cures were reported in human tests, and mass production was finally achieved USDA North Regional Research Lab One team of researchers was looking for more high-yielding sources of penicillin Moldy fruits and vegetables were routinely collected from local groceries stories Fungi were isolated and tested for antibiotic production Summer of 1943 Cantaloupe was found contaminated with Penicillium chrysogenum. The fungus produced 200 times more penicillin than Flemings isolate. This species was used in the industrial production of the drug and continues to be used today Mass Production Achieved By D-Day in 1944, there was enough penicillin to treat all British and American casualties of the European invasion By the time World War II ended, sufficient penicillin was available for civilian use In 1945 Florey, Chain, and Fleming received the Nobel Prize for their work in developing the first “miracle“ drug 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 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 Flemings original isolate Drawbacks - 1: Resistance Over-prescribing by physicians and veterinarians commonly occurs Antibiotics were incorporated into animal feed for use in feedlots Widespread use led to the evolution of penicillin-resistant bacteria Rise of Resistant Bacteria Bacteria reproduce every 20 min Time-table for the evolution of new strains faster than other organisms By the early 1960s resistance was evident among many types of bacteria By the early 1990s antibiotic resistance has become a major cause for concern among the medical community Drawback-2: Allergies Small percentage of population is allergic Can result in severe or even fatal anaphylactic reactions Penicillin is the most frequent cause of anaphylaxis Several hundred die each year from anaphylaxis due to penicillin allergy 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 b Lactam Basic Structure 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 Penicillin-G Penicillin-G Still an important antibiotic Disadvantage has been that it is unstable in acid conditions Given by injections - otherwise stomach acids would destroy 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 Penicillin-V phenoxy methyl penicillin Semi-Synthetic Penicillins A strain of Penicillium chrysogenum 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 versatile group of antibiotics 6-APA Ampicillin Methycillin R=H 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 is bacterial wall is weakened and cell explodes from osmotic pressure b-Lactamase Within a decade of the introduction of penicillin, resistance was starting to develop Resistance due to the presence of an enzyme that cleaved the b-lactam ring - enzyme called b-lactamase By late 1950s looked like penicillin would dimish in importance b-Lactamase Cephalosporin In 1948 Giuseppe Brotzu, an Italian microbiologist identified a compound produced by Cephalosporium acremonium that was an effective treatment for gram- positive infections as we