MICR J210 1st Edition Lecture 5 Outline of Last Lecture I. Metabolisma. Aerobicb. AnaerobicII. DNA Replication in Prokaryotesa. Protein Synthesis III. Bacterial GrowthIV. Bacteria and Patient CareOutline of Current Lecture I. Antibiotic Action and Geneticsa. Historyb. Side effectsII. Normal FloraIII. Drug Resistance IV. Mechanisms of Gene Transfer in BacteriaV. Recombinant DNA TechnologyCurrent LectureAntibiotic Action and Genetics- The First Antibiotico Penicillin was discovered by Alexander Flemingo While working with Staph. aureus, a fungi spore accidentally dropped onto his petri dish This fungus, Penicillium, secreted a substance that is destructive to bacteria - No colonies of bacteria were growing adjacent to the mold- Efforts to produce large amounts of mold failed for 10 yearsThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- Flory and Chain were able to produce the antibiotic penicillin in large quantities He also discovered the antibacterial substance lysozyme which is present in human tears and saliva - Antibioticso Against living organism- Antimicrobialo Against microbes- Narrow spectrumo Effective against only a limited range of organismso Example: a drug has a narrow spectrum if it only can target gram + bacteria- Broad spectrumo Refers to antibiotics with activity against a wide range of organismso Example: a drug has a broad spectrum if it can target both gram + bacteria and gram – bacteria- Bactericidalo Drug that completely destroys bacteriao Cidal=death Drugs works by irreversibly biding to active site of enzymes that link peptidoglycan molecules Why does this kill the bacterial cell?- If the drug blocks the biosynthesis of PG, then the cell will become extremely thin and the cell will burst due to the fact thatthe PG is too thin to support the pressure inside the cell- Antibiotics interact with the transpepdidases and prevents the formation of the NAM-NAG peptide linkage during PG synthesis Penicillin works best with gram + bacteria because they are coated with an outside layer of peptidoglycan unlike gram – bacteria in which the outer layer is a phospholipid membrane - Bacteriostatico Drug which stops cell growth but does not completely kill the bacteriao Example: Erythromycin Drug binds to subunits of bacterial ribosomes and stop bacterial protein synthesis which then stops growth of bacteria without destroying them If you block protein synthesis pathways in bacteria then they won’t be able to replicate themselves Bacteria will be stuck in the S phase (DNA synthesis phase) and won’t beable to duplicate themselveso If the drug stops the growth of the bacteria, then the human immune system can take over and kill them If the immune system doesn’t kick in, then once bacteria are inoculated with nutrients and the bacteriostatic drug is dilated, they will resume normal growth Never give a bacteriostatic drug to an immunosuppressed patient- Antibiotics are often derived from microbial specieso Semisynthetic: a molecule derived from a biological source and manipulated in the laboratory to improve characteristics; derived from nature and made in the laboratoryo Microbes develop antimicrobial properties to compete for food and living space Many antibiotics are developed from these microbes You can chemically derive the molecule to make them more soluble or more effective as a drug (try to improve on the natural product)- Selective toxicityo Toxic to one thing but not anothero A good antibacterial drug should be highly toxic to bacteria but non-toxic or close to non-toxic to humans Does not cause serious side effects- Unique targeto Basis for selective toxicity The bacteria needs to have something unique that the host doesn’t have so that you can destroy that target and the bacteria without harming humans Works well because prokaryotes are very different from humans- Harder with fungi—fungi are eukaryotes and more similar to humans so finding unique targets is more trickyo A site in pathogen that is infecting the patient that drug needs to work specifically that is not present in the patiento Example, penicillin targets peptidoglycan which is present in bacteria onlyo A reason we need to compare prokaryotes and eukaryotes in detailo Cell Wall Synthesis Inhibitors (Cidal) Beta Lactams: lactam ring binds to the transpeptidases and blocks the enzymes from laying down more peptidoglycan- Penicillin- Cephalosporins Vancomycin (blocks cell wall synthesis in gram +) Bacitracino DNA Synthesis Inhibitors (Cidal): binds to DNA gyrase which is in prokaryotes but not in eukaryotesthis disables the cell from being able to unwrap the DNA so protein synthesis is stopped Quinolones Metronidazoleo RNA polymerase inhibitor (Cidal): blocks transcription Rifampino Plasma membrane Inhibitor (Cidal): prevent the cell membrane from forming or perturb its structure Polymyxinscan also destroy mammalian cells so it is only used topically, never injected or swallowedo Protein Synthesis Inhibitors (Static): bind to bacterial ribosomes and block protein synthesisthey bind irreversibly so bacteria stop in their tracks[However, if the concentration of drug drops, the bacteria from new ribosomes and keep growing] Erythromycin Chloramphenicol Tetracyclineo Antimetabolites (Static): target the biosynthesis of folic acid (essential metabolite for bacteria)can resume growth and production of folic acid once concentration of drug goes down Folic acid synthesis inhibitors- Sulfonamides- Prophylaxiso Preventative measureso Example: if a patient has a history of rheumatic fever, a prophylactic measure would be to give the antibiotics before dental or surgical proceduresSide Effects of Antibiotics- Allergieso Penicillin Some patients have a hypersensitivity which can lead to shock and deatho All drugs have the potential to cause allergies- Organ toxicityo Vancomycin: neurotoxic and nephrotoxic Used to treat drug resistant Staph.o Chloramphenicol: Immunotoxicity Depresses immune systemo Bacitracin: Nephrotoxic Only use topicallyo Tetracycline: complexes with calcium and causes abnormalities in bone and teeth Avoid giving to children and pregnant womenNormal Flora- Commensal flora is all the natural bacteria that live in and on a healthy person- 100 trillion bacteria can be in one