1. MICROBIOLOGY – ALCAMO LECTURE: Chemotherapeutic Agents and Antibiotics

2. For centuries, doctors thought that drastic measures were necessary to save a patient from infectious disease: – ____________ and ____________ – Large doses of chemicals – Ice water baths – ____________ – These treatments probably made a bad situation worse

4. Chemotherapeutic Agents and Antibiotics In 1825, doctors in Boston and London wanted to see what would happen if these treatments were not given They found that no treatment at all was better For the next 60 years it became the doctor’s job to ________________________, explain it to the family, and sit by caring for the patient

5. Chemotherapeutic Agents and Antibiotics Late 1800’s – ____________ ________________________ Doctors understood where disease comes from but could do little Tuberculosis killed 1 of every 7 people that died Streptococcal heart valve disease, pneumonia, and meningitis ____________

8. Chemotherapeutic Agents and Antibiotics 1940’s – chemotherapeutic agents and ____________ were discovered Doctor’s learned that they could kill ____________ in the body without harming the body itself Doctors were altering the course of ____________ which made a dramatic change in the world

13. Chemotherapeutic Agents & Antibiotics Must be more ____________ to MO than host cells ____________ only helps the immune system to control the infection The immune system ultimately stops MOs

14. Chemotherapeutic Agents Produced in lab, inorganic chemicals Sulfur, Arsenic, Quinine, Nicotinic Acid Still major medical applications Can be quite ____________ to patient

15. Antibiotics Originally: Chemical produced by an MO which ____________ ____________of other MOs Now synthesized in labs, Organic Chem

17. Chemotherapeutic Agents & Antibiotics Have ____________ ____________ mechanisms Select for specific MO according to which life process you need to disrupt: – ____________ ____________ – Cell Wall structure – ___________ ____________ ____________ – RNA or DNA synthesis – Chemical ____________

19. History of Chemotherapy Paul ____________ – worked with stains and dyes and found out they had antimicrobial properties Collaborated with Sahachiro Hata to produce Salvarsan – 1 st chemotherapeutic drug (___________ ) Problems: – Local reaction at injection site – Church wanted ____________ to be a deterrent to immoral behavior

20. History of Chemotherapy For the next 20 years, German scientists kept testing dyes for ____________ ____________ Gerhard Domagk tested prontosil dye on his own daughter when she became ill with ____________ and she recovered

21. Sulfa Drugs It was determined that the active ingredient in prontosil is ____________ In 1940, D.D. Woods and E.M. Fildes proposed a mechanism of action for ____________ ____________ It showed how they could interfere with ____________ ____________ without damaging host tissues

22. Competitive Inhibition Bacteria need folic acid to produce nucleic acids (____________________ ) Bacteria have an ____________ to make folic acid – they can’t get folic acid from ____________ like we do This ____________ joins PABA with 2 other components to make folic acid Sulfanilimide looks like PABA and ____________ will bind to it instead of PABA

24. Sulfa Drugs ____________ : – Sulfamethoxazole – Used for urinary tract infections and pneumonia ____________ : – Sulfisoxazole – Used for vaginal infections, conjunctivitis and toxoplasmosis

25. Antibiotics Word means “___________ _________ ” Chemical products or derivatives of certain organisms that are ____________ to other organisms How did organisms gain the ability to produce __________? – Random genetic mutation – Evolutionary advantage

26. Antibiotics Mainstay for help with ____________ ____________. Used for some fungal and protozoal infections Useless on ____________ (2ndary Bact Inf) Usually ____________ / ____________, some patients dangerously hypersensitive

27. Alexander Fleming Discovered ____________ One of his agar plates containing staphylococci became contaminated with a green mold He noticed the staphylococci didn’t __________ ____________ ___________ He identified the mold as a species of ____________ and he named its substance penicillin

28. Zone of Inhibition

29. Penicillin Isolated from a fungus - ____________ First antibiotic, 1940’s Interferes with cell wall synthesis Effective against G+ MOs Few G- with massive doses “____________ : a very large family of drugs

30. This bacterium is lysing because an antibiotic disrupted its cell wall. Why doesn’t the antibiotic lyse human cells?

31. Disadvantages of Penicillin 1. ____________ or allergy – Swelling of the eyes or wrists – Flushed or itchy skin, hives – Shortness of breath 2. ____________ ____________ bacteria – Produce ____________, an enzyme that converts penicillin into a useless compound – Use too many ____________ – natural selection of antibiotic resistant bacteria

32. Semi-synthetic Penicillins In the 1950’s the beta-lactam nucleus of the ____________ molecule was identified and synthesized New ____________ were created by attaching different groups to this nucleus: ____________

33. Cephalosporin Isolated from a ____________ - Cephalosporium Interferes with ____________ ___________ Similar to ____________ – can be used in allergic persons and with resistant MOs Interferes with some G+ and some G- MOs

34. Streptomycin Isolated from a filamentous (mold-like) soil bacteria - ____________ ____________ Attaches to ____________, blocks messenger RNA Carefully used, toxic side effects (____________ ) “____________ ” a very large family of drugs – Neosporin contains Neomycin

35. Chloramphenicol Streptomyces’ 2 nd family of drugs: Original Prod: Chloromycetin 1 st “____________ ____________ ” Antibiotic Wide variety of G+ and G- MOs Interferes with protein synthesis, ____________ blocked from mRNA

36. Tetracycline ____________ ____________ antibiotics Can be taken orally and were used widely in the 1950’s and 1960’s Overused, so __________ ________was eliminated from the intestines Then ____________ (Candida albicans) flourished and antifungal antibiotics had to be taken Also caused gray-brown tooth ____________

37. Antimicrobial Drugs ____________ : The use of drugs to treat a disease ____________ ____________ : Interfere with the growth of microbes within a host ____________ : A substance produced by a microbe that, in small amounts, inhibits another microbe ____________ ____________ : A drug that kills harmful microbes without damaging the host

38. The Action of Antimicrobial Drugs ____________ – Kill microbes directly ____________ – Prevent microbes from growing

39. Antibiotic Assays 1. ____________ ____________ ____________ – determines the smallest amount of antibiotic necessary to inhibit a test organism – Prepare a set of tubes with different ____________ of an antibiotic – The tubes are ____________ with the test organism, incubated and examined for growth – Extent of ____________ gets lower with increasing concentration of antibiotic – When growth ____________ to occur – you have reached the minimum inhibitory concentration (MIC)

41. Antibiotic Assays 2. Agar or disk ____________ ____________ – operates on the principle that antibiotics will diffuse from a paper disk into agar medium containing test organisms – ____________ ____________ as a failure of an organism to grow in the region of the antibiotic

42. Kirby-Bauer Test 1. ____________ ____________ into plate and inoculate with test organism 2. ____________ ____________ ____________ containing known concentrations of antibiotics to the surface 3. ____________ plate 4. ____________ ____________ of zones of inhibition to a standard table to determine if test organism is susceptible **If organism is susceptible, it will be killed in patient’s blood stream if experimental concentration of antibiotic is reached

43. The Disk-Diffusion Method

44. Antibiotic Resistance and Abuse During past 25 years, a large # of bacterial species have evolved with ____________________________________ ____________ organisms are responsible for human diseases in: – Intestines, lungs, skin, urinary tract Common diseases that used to be easy to treat with a single dose of ____________ are now hard to treat: – Bacterial pneumonia, strep throat, gonorrhea

45. Antibiotic Resistance and Abuse How do MOs ____________ ____________ ?: – Production of ____________ capable of destroying antibiotic (penicillinase) – Changes in ____________ of cell wall – ____________ to drug’s activity by bypassing a normal metabolic pathway and creating an altered one (new way to produce folic acid)

47. Antibiotic Resistance and Abuse ____________ ____________ may develop: – Normally - mutation – From doctors prescribing too many antibiotics – forced evolution – From hospitals using too high doses of post- surgery antibiotics – forced evolution – From livestock feeds which contain 40% of all antibiotics produced in U.S. – forced evolution

48. Antibiotic Resistance and Abuse Can resistance be transferred?? Researchers ____________ ____________ antibiotic resistance genes from one bacterial species to another using plasmids There is potential for the transfer of antibiotic resistance from a harmless bacterium to a pathogenic bacterium Result – ____________ ____________

50. Antibiotic Resistance and Abuse ____________ have been known as miracle drugs – they are overworked miracles Suggestions have been made to ____________ their use as strictly as narcotics are controlled But, antibiotics are ____________ in 3 rd world countries where they are sold over-the- counter