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huelsenbeck 1-2

huelsenbeck 1-2 - Lectures 1 2 Friday Monday March 2 2009...

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Lectures 1 & 2 Friday, February 27, 2009 & Monday, March 2, 2009 An example of the relevance of evolution today The usual story is that Alexander Fleming accidentally discovered penicillin; the story is that Fleming, working in St. Mary’s hospital in London, was working with a culture of Staphylococcus aureus , a pathogenic bacterium on which he was doing some research, when he noticed that it had become contaminated by a species of Penicillium . He noted that the mold was inhibiting the bacterial growth. He writes a paper on his finding in 1929, and the rest is history. The actual story is a little bit different. Fleming was searching for antibacterial agents as early as 1920, and was largely motivated by his World War I experience where he witnessed the deaths of many soldiers from septicemia (blood poisoning). In 1922 Fleming discovered lysozyme (an enzyme that lyses bacteria). In 1928, while researching staphylococci, he benefited from chance, and a well conditioned mind that was looking for agents that inhibited bacteria. His lab, evidently, was not a very orderly one, and cultures he worked on were often forgotten, and hence contaminated eventually. After returning from a month-long vacation, Fleming found many of his plates contaminated with a fungus. He noticed a zone of inhibition around the fungus. He thought he was on to something, and eventually isolated an extract from the mold that, by itself, could inhibit the growth of bacteria. He named the inhibitor ‘Penicillin’. By 1943, drug companies were mass-producing penicillin for the war effort. Thousands of lives were saved by this “miracle drug” over the course of the war. And of course, the lives of perhaps millions of people were saved by penicillin and related drugs after the war. For us, it is difficult to imagine living in dread of dying of a bacterial infection, of any kind. But, of course, this was not always the case. The last 50 years has been termed a golden age in medicine, mostly because of the better treatment of bacterial pathogens. 1943 marks the beginning of the antibiotic error. 1947, however, marks the beginning of the emergence of antibiotic resistant bacteria. 1947 saw the first penicillin resistant pathogen, Staphylococcus aureus . By 1967 penicillin resistant pnemococci had surfaced and American military personnel in Southeast Asia were starting to bring home penicillin resistant gonorrhea. The response by the medical community was a natural and reasonable one. If penicillin doesn’t work as effectively, let’s find another antibiotic. The 1950’s saw chloramphenicol, neomycin, streptomycin, tetracycline, erythromycin and cephalosporins added to the list of antibiotics. The 1960’s saw the addition of several new aminoglycosides, but resistance to one aminoglycoside was often accompanied by resistance to other aminoglycosides. (An aminoglycoside acts by tightly binding to a structural component of the 30S ribosomal subunit to inhibit protein synthesis.) The 1970’s were bleak in terms of adding new antibiotics, but the 1980’s saw the addition of an important new class of antibiotics called the fluoroquinolones, of which Ciprofloxacin
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is probably the most familiar. (Fluoroquinolones inhibit gyrase in bacteria, which is an
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