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Similar to first lecture natural antibiotics.ppt
first lecture natural antibiotics.ppt
- 1. ANTIBIOTICS From the Greek: anti- against bios - life
- 2. Chemotherapy • Paul Ehrlich •Use of chemical agent to kill bacteria and not harm the host • Search for the “Magic bullet” • Developed an arsenic compound that killed the bacteria that causes syphilis • Compound was called salvarsan but was quite toxic to the host
- 3. Antibiotics • Natural compoundsproduced by microorganisms that inhibit the growth of other microbes • Majority of antibiotics come from Streptomyces bacteria and molds • Over 100 different antibiotics • Antibiotics generally have two names – Brand name created by the drug company – Generic name based on the chemical structure or class of antibiotics
- 4. HISTORICAL PERSPECTIVES • Thediscovery of the first antibiotic was an accident. – Alexander Fleming accidentally contaminated a plate with a fungus. – He observed a clearly defined region of no bacterial growth where the fungi had contaminated the plate. – The area around the fungus was eventually referred to as a zone of inhibition.
- 5. …HISTORICAL PERSPECTIVES • It isestimated that over 80 million prescriptions are written in America each year. • 12,500 tons of antibiotics are produced annually. – 25-50 % is fed to livestock to increase the rate of weight gain. • From 1900 to 1980, mortality from infectious diseases dropped from 797 per 100,000 persons to 36 per 100,000 persons.
- 6. …HISTORICAL PERSPECTIVES • Nomajor discoveries of natural antibiotic substances have occurred for several years. – Efforts have now shifted to modifying existing antibiotics. – Searching in new places for potential antibiotics has also gained in prominence. • Many antibiotics are produced by microorganisms as part of their survival mechanism. – They keep other organisms away. – They protect the supply of nutrients and oxygen.
- 7. ANTIBIOTICS ARE PARTOF BACTERIAL SELF PROTECTION • Microorganisms that produce these substances have molecular mechanisms to control production and prevent self-destruction. • Naturally produced antibiotics are products of secondary metabolic pathways. – These pathways are not turned on all the time. – Continuous production could adversely affect the organism. – Some bacteria restrict antibiotic production to the stationary phase. – Others keep the intracellular concentrations at low levels.
- 8. …ANTIBIOTIC SPECTRA • Thefirst molecules that inhibited bacterial growth were natural products. • Over time, these natural molecules have been modified. • Several types of semi-synthetic antibiotics have been derived from these molecules.
- 9. …ANTIBIOTIC SPECTRA • Theoriginal natural molecules used by humans as antibiotics have a very narrow spectrum. – Penicillin activity is restricted to Gram-positive bacteria. • Natural molecules can be chemically modified making it possible to broaden their spectrum. • Antibiotics are classified as either broad- spectrum or narrow-spectrum.
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- 11. Alexander Fleming • Discoveredpenicillin by accident in 1928 • A mold contaminating a plate of Staphylococcus aureus showed anti-bacterial properties • The mold was identified as a member of genus Penicillum, hence the name for the naturally produced antibiotic • Fleming won the Nobel prize in 1945 for this discovery, shared with Howard Florey and Ernst Chain
- 12. Penicillin • Wonder drug •Killed bacteria with few side effects on the patient • SELECTIVE TOXICITY • Penicillin was NOT the first anti-bacterial compound • Penicillin was the FIRST natural compound that kills bacteria • Antibiotic • Not made in the lab
- 13. How do antibioticswork?
- 14. Cell Wall Synthesis •Penicillin • Prevents synthesis of the peptidoglycan components of the cell wall • Targets actively growing cells • Very little toxicity to human cells
- 15. Inhibition of proteinsynthesis • Broad spectrum of activity – all bacteria have to make proteins • Difference in ribosome size in bacteria accounts for selective toxicity • Chloramphenicol, erythromycin (G+), streptomycin, tetracyclines
- 16. Injury to plasmamembrane • Changes to permeability of membrane causes loss of metabolites • Polymyxin B
- 17. Inhibition of nucleicacid synthesis • Inhibition if either DNA replication or mRNA synthesis • Toxicity problems • Rifampin – mRNA blocker • Nofloxacin and ciprofloxacin – DNA synthesis blockers
- 18. Inhibition of synthesisof essential metabolites • Block enzyme activity • Competitive inhibition of enzyme activity • PABA (para-aminobenzoic acid) competition • Sulfonamides
- 19. Metabolite Inhibition • Sulfonamide• P-aminobenzoic acid
- 20. Commonly used antibiotictypes • Penicillins • Cephalosporins • Animoglycosides • Macolides • Sulfonamides • Fluoroquinolones • Tetracyclines • Polypeptides
- 21. Penicillin • Destroys thecell wall of bacteria • Best against G+ bacteria during active growth • Examples: – Penicillin G – Penicillin V – Ampicillin – Amoxicillin
- 22. Cephalosprorins • Similar topenicillin - interferes with cell wall formation • Used when patient is allergic to penicillin • Examples – Cefadroxil – Cephapirin – Cephalexin – Cephalothin
- 23. Aminoglycosides • Inhibition ofprotein synthesis in bacteria • Some toxic reactions possible in kidney and liver • Examples – Gentamicin – Streptomycin – Neomycin
- 24. Macrolides • Interfere withbacterial protein synthesis • Commonly given to patients that are sensitive to penicillin • Gastrointestinal discomfort is a common side effect • Examples – Azithromycin – Erthromycin
- 25. Sulfonamides • Very earlyantimicrobial substance • Commonly called sulfa drugs • Developed in the 1930’s in Germany • Mode of action is enzyme inhibition • Allergy to sulfa is common
- 26. Fluoroquinolones • Large classof semi-synthetic broad spectrum antibiotics • Inhibition of bacterial DNA replication • Few side effects, well tolerated • Examples – Ciprofloxacin – Norfloxacin
- 27. Tetracycline Antibiotics • Membersof this group of antibiotics are produced by Streptomyces group of bacteria • Inhibition of protein synthesis • Used commonly to treat acne • Examples – Tetracycline – Deoxycycline
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- 30. Cephalosporin and Penicillin •Cephalosporin • Produced from a fungus • Similar in action to penicillin • More active against G- bacteria • More resistant to penicillinase • Penicillin • Produced from fungus • Inhibits cell wall synthesis • Effective against mostly G+ bacteria • Penicillinase sensitivity
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- 32. Adverse reactions • Toxicity •Allergy • Disruption of natural flora – Yeast infections
- 33. Antibiotic Resistance (A BIGproblem) • Resistance is acquired by mutation • R (resistance) plasmids acquired by bacterial conjugation • How to limit resistance – Take all your pills, don’t stop when you feel better – Use antibiotics only when necessary – NEVER take antibiotics for viral infection alone
- 34. Nosocomial Infections • Infectionsacquired while in a health care facilities • CDC estimates 2 million people per year get these infections • 90,000 deaths per year
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- 36. Antiviral Drugs • Limitedin number • Targets for these drugs are viral reproduction • Nucleotide analogs are the most commonly used agents – disrupt viral nucleic acid replication • Acyclovir
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