Antimicrobial Drugs(Chapter 20)Lecture MaterialsforAmy Warenda Czura, Ph.D.Suffolk County Community CollegeEastern CampusPrimary Source for figures and content:Tortora, G.J. Microbiology An Introduction 8th, 9th, 10th ed. San Francisco: PearsonBenjamin Cummings, 2004, 2007, 2010.Amy Warenda Czura, Ph.D.1SCCC BIO244 Chapter 20 Lecure SlidesSelective toxicity = kill pathogen without harming hostChemotherapy = treatment with chemical substancesAntibiotic = substance produced by microbesthat inhibits or kills other microbesFirst: Penicillin, Fleming 1928Antibiotic producers:Streptomyces speciesBacillus speciesPenicilliumCephalosporiumAmy Warenda Czura, Ph.D.2SCCC BIO244 Chapter 20 Lecure SlidesAntimicrobial drugs = both antibiotics and synthetic chemotherapySpectrum of microbial activity = range of microbial types affected by particular antimicrobiale.g Penicillin → Gram +(Gram negative more resistant in general:outer membrane only allows substancesthrough porins, drug has to be small to pass)Broad spectrum “antibiotics”:-work on wide range of bacteria-tend to kill off normal flora/microbiota-can lead to superinfection:Superinfection = one remaining organism takes over and causes disease, usually multi-drug resistantAntibacterial drugs are1. Bactericidal = kill bacteria directly2. Bacteriostatic = prevent bacterial growth sohost immune defenses can kill itAmy Warenda Czura, Ph.D.3SCCC BIO244 Chapter 20 Lecure SlidesModes of Action of Antibacterial Drugs:*best drugs target bacterial specific feature sotoxicity to humans is low1. Inhibition of cell wall synthesis-peptidoglycan not found in humans-can inhibit NAG and NAM synthesis or crosslinking-only affects actively growing cells: new wallsthin and weak2. Inhibition of protein synthesis-eukaryotes = 80s ribosome, prokaryotes = 70s-can target 70s but toxicity to mitochondria-inhibit peptide bond formation, attachment oftRNA, or cause misreading of mRNAAmy Warenda Czura, Ph.D.4SCCC BIO244 Chapter 20 Lecure Slides3. Injury to plasma membrane-alter permeability = loss of metabolites-all membranes similar: toxicity riskAmy Warenda Czura, Ph.D.5SCCC BIO244 Chapter 20 Lecure Slides4. Inhibition of nucleic acid synthesis-interfere with DNA replication or transcription-all cells similar enzymes and nucleotides: toxicity risk5. Inhibit synthesis of essential metabolites-drug = competitive inhibitor of enzyme in metabolite synthesis pathway(metabolite = any organic needed for growth)-must target bacterial specific pathwaysAmy Warenda Czura, Ph.D.6SCCC BIO244 Chapter 20 Lecure SlidesTests to guide chemotherapy:-different species have different susceptibilities-resistance can appear over time-must choose right drug in right concentration1. Disk-diffusion/Kirby-Bauer test-to determine which drug microbe is most susceptible tomethod:-plate lawn of bacteria-place disks of known antimicrobials on lawn-measure zones of inhibition, compare to resistance chart to choose bestAmy Warenda Czura, Ph.D.7SCCC BIO244 Chapter 20 Lecure Slides2. E-test-to estimate MIC (minimal inhibitory concentration) for effective dosemethod:-plate lawn-apply strip with concentration gradient ofantimicrobial-read minimum level that inhibits growthAmy Warenda Czura, Ph.D.8SCCC BIO244 Chapter 20 Lecure Slides3. Broth Dilution Test-to determine MIC and MBC (minimal bactericidal concentration)-differentiate bacteriocidal versus bacteriostatic drug actionmethod:-create sequence of decreasing concentration of drug in broth-inoculate test bacteria-test no growth wells for live bacteria in drug free media: growth = static (MIC)no growth = cells dead = cidal (MBC)Common Drugs (on handout)Amy Warenda Czura, Ph.D.9SCCC BIO244 Chapter 20 Lecure SlidesMechanisms of Drug Resistance1. destruction/inactivation of drug2. prevent penetration to target site in cell3. alteration of drug target site4. rapid efflux (pump out of cell before drug finds target)*resistance is passed on plasmids: gene toproduce protein that will do one of the above,(typically mechanism #1 or 4)Amy Warenda Czura, Ph.D.10SCCC BIO244 Chapter 20 Lecure