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Part II: How are antibiotics discovered? 12 classes of antibiotics were discovered before 1970 and since then only two. Year Introduced 1935 1941 1944 1945 1949 1950 1952 1956 1957 1959 1962 1968 1969 2000 2003 Class of Drug Sulfonamides Penicillins Aminoglycosides Cephalosporins Chloramphenicol Tetracyclines Marcolides Glycopeptides Rifamyxins Nitroimidiazoles Quinolones Trimethoprim ‘We can close the books on infectious diseases', US Surgeon General Oxazolidinones Lipopeptides The rise of antibiotic resistance has made it important to discover new antibiotics. These activities explore that topic. 1) First watch the video: The discovery of antibiotics. http://www.pbs.org/wgbh/rxforsurvival/series/video/d_pne1_dis_pneu2_qt_h.html Why do you think molds produce penicillin? What is the target of penicillin? 2) Listen to the podcast by one of the authors of a paper which came out in October, 2008. http://www.sciencefriday.com/program/archives/200810175 Click on the arrow under ‘Listen’ on the left side of the page. Where were these antibiotics found? Why do they think they are produced by soil organisms? What needs to be done before these antibiotics are ready for human use/testing? Why is RNA polymerase a good target for treatment of tuberculosis? What is the structural mechanism of action? Why do you think combination therapy is effective in avoiding antibiotic resistance? 3) Finally, read the review of the original paper (Tie me up, Tie me down: Inhibiting RNA polymerase) and answer the following questions briefly. Come to class tomorrow with any questions you have about this paper. a) Explain how a search for resistant mutants can give information as to the antibiotic’s target and mechanism of action. b) By adding the antibiotic (myx) at different times in a transcription reaction, the authors showed that myx inhibits RNA polymerase binding to double stranded DNA. Explain.