Download Part II: How are antibiotics discovered

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.