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Chapter 6: The Elements of Chemotherapy

by: Siân L'Roy

Chapter 6: The Elements of Chemotherapy 2420

Marketplace > Tarrant County College District > Biology > 2420 > Chapter 6 The Elements of Chemotherapy
Siân L'Roy


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This chapter covers the history of antibiotics and how some bacteria can become antibiotic resistant to one or many medical drugs.
Mark Pulse
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This 4 page Class Notes was uploaded by Siân L'Roy on Sunday August 21, 2016. The Class Notes belongs to 2420 at Tarrant County College District taught by Mark Pulse in Summer 2016. Since its upload, it has received 4 views. For similar materials see Microbiology in Biology at Tarrant County College District.


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Date Created: 08/21/16
The Elements of Chemotherapy (Antibiotics)  Alexander Fleming was one of the first scientist to recognize the importance of antibiotic  treatment for life­threatening infections o In 1928 he observed a fungal contaminant that inhibited the growth of S. aureus  on plate cultures o He determined the fungus to be a species of Penicillium; he identified the new  inhibitory agent as pencillin o Fleming observed that penicillin was effective against several species of bacteria,  and was minimally toxic to the host (animals) o He was not able to successfully purify penicillin; this was accomplished by Chain  and Florey in the 1940’s  Penicillin was mass produced for use in WWII  Prior to penicillin, more soldiers died from wound­associated infections than from the  instruments of war (bullets) themselves   In 1900, 1 out of 100 infected individuals died in the United States; by 1990, the  frequency dropped to 1 in every 300 infected individuals Sir Alexander Fleming (1881­1955)  Lecturer at Saint Mary’s Medical School (London, England)  Research focused on identifying products that inhibited bacterial growth  Discovered lysozyme in 1923 (hydrolyzes cell walls)  Accidently discovered penicillin in 1928 o Penicillin Discovery  He noticed that Staphylococcus aureus growth was inhibited near a mold  contaminant  He identified the mold as a Penicillium notatum  Named the inhibitory agent of penicillin  Published findings in the British Journal of Experimental Pathology in  1929  Fleming was not able to successfully purify penicillin in the lab Howard Florey and Ernest Chain  Headed research team at Oxford University in England The Elements of Chemotherapy (Antibiotics)  Selected penicillin in 1938 as a possible treatment for bacterial infections   Designed a method to purify penicillin in 1940  Performed animal test to validate the activity of penicillin within an infected host o Early uses of purified penicillin  First human patient dosed with penicillin in February 1941 (Albert  Alexander)  Five patients with infections dosed with penicillin  4 out of the 5 fully recovered  Results published in 1941 (The Lancet)  Full industrial scale up in the United Kingdom and the United States  Penicillin was available on D­Day (WWII) landing in June 1944  Based on their macromolecular activities, most antibiotics belong to 1 of 6 antibiotic  classes 1. Cell wall synthesis inhibitors: Includes β­lactams (penicillin), glycopeptides  (vancomycin), bacitracin, and phosphonomycin; all prevent the formation of  the cell wall in dividing cells 2. Protein synthesis inhibitors: Includes aminoglycosides (gentamicin),  tetracyclines (tetracycline), and macrolides (erythromycin); all directly inhibit  protein synthesis by binding to the ribosome 3. DNA replication inhibitors: Includes fluoroquinolones (ciprofloxacin) and  metronidazole; fluoroquinolones bind to DNA gyrase to prevent DNA  replication, while metronidazole generates nicks in a DNA strand 4. RNA synthesis inhibitor: Only rifampin belongs to this class; it binds to  RNA polymerase and blocks transcription 5. Tetrahydrofolic acid synthesis inhibitors: Includes trimethoprim and  sulfonamides; both are competitive inhibitors of tetrahydroflic acid production (needed for nucleic acid and fMet synthesis) 6. Cytoplasmic membrane damager: Daptomycin belongs to this class; it binds to and damages the cytoplasmic membrane of Gram (+) bacteria What is antibiotic resistance?  The Elements of Chemotherapy (Antibiotics)  An antibiotic cannot inhibit the growth of or kill bacteria  Generated due to selective pressure associated with the over use of antibiotics  It is a matter of survival for the  bacterial cell Alexander Fleming warned of resistance developing to penicillin in his Nobel Prize Lecture in  1945, stating that, “It is not difficult to make microbes resistant to penicillin in the laboratory by  exposing them to concentrations not sufficient to kill them, and the same thing has occasionally  happened in the body.” By 1960 more than 80% of Staphylococci were resistant to penicillin **Bacteria are not just resistant to one antibiotic, but many are Multi­Drug Resistant organisms  (MDR)  Antibiotic resistance has become more prevalent as a result of their use in medicine and  other industries (agriculture)  Resistance can be innate or acquired, and several mechanisms of resistance have been  identified in bacteria  Identified mechanisms of resistance include: o Production of drug inactivating enzymes  E.g.: penicillinase is produced by bacteria (mostly Gram negative) that  enzymatically inactivates penicillin o Modification to the target molecule or pathway  E.g.: penicillin can no longer recognize modified penicillin­binding  proteins (PBPs) involved in cell wall synthesis o Decreasing the influx/uptake of an antibiotic  E.g.: Gram­negative bacteria can alter the structure of membrane­ associated porins (channels), effectively reducing the influx of an  antibiotic o Increased elimination of internalized drug  E.g.: Bacteria can up­regulate (increase) the numbers of an efflux pump  involved in ‘pumping’ an internalized antibiotic out of the cell The Elements of Chemotherapy (Antibiotics)  Antibiotic resistance in bacteria can be acquired by spontaneous genetic mutations or by  the horizontal transfer of resistance genes


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