Antimicrobial Agents and Therapy Don t need to memorize Structures Antimicrobial Agents and Therapy Definitions see Table 12 2 o Chemotherapeutic Drug a chemical used in the treatment of disease Ex Anti cancer drugs o Antimicrobial Drug a chemical used in the treatment of infectious Antibacterial antiviral antifungal etc a type of antimicrobial drug which is natural product of a disease o Antibiotics living organism Prime drug What Organisms Produce Antibiotics Certain types of bacteria and Fungi Phylum Actinobacteria o Gram abundant in soil and water The most common group known as The Actinomycetes o General characteristics Most aerobic chemoheterotrophs Many produce branching tube like cells hyphae that often form interconnected networks mycelia Some produce spores Many free living a few are pathogens Importance of Actinomycetes Free living forms common in soils o Streptomyces and antibiotic production Number of antibiotics produced Don t need to memorize numbers Microorg anisms YEAR TOTAL STREPT OMYCE TES RAREFO RMS BACTER IA FUNGI Before 1940 1945 1950 1955 1960 1965 1970 1975 1978 5 88 316 707 1275 1898 2889 4099 4973 2 10 72 325 760 1177 1745 2361 2769 2 10 22 40 75 136 250 396 2 25 94 137 181 223 328 518 567 1 51 140 223 294 423 680 970 1151 Types of Antibiotics Produced Don t need to memorize shows that the type is very specific ANTIBIOTIC ISOLATED FROM MICROORGANISM Spectrum Broad Narrow ACTIVE AGAINST BLASTICIDIN S STREPTOMYCES GRISEOCHROMOGENES FUNGI CHLORAMPHE NICOL STREPTOMYCES VENEZUELAE GRAM POSITIVE NEGATIVE BACTERIA CYCLOHEXIMI DE STREPTOMYCES GRISEUS FUNGI ERYTHROMYC IN STREPTOMYCES ERYTHREUS GRAM POSITIVE BACTERIA KANAMYCIN STREPTOMYCES KANAMYCETICUS GRAM POSITIVE NEGATIVE BACTERIA STREPTOMYCI N STREPTOMYCES GRISEUS NEOMYCIN STREPTOMYCES FRADIAE TUBERCULOSIS BACTERIA GRAM POSITIVE NEGATIVE BACTERIA TUBERCULOSIS BACTERIA GRAM POSITIVE NEGATIVE BACTERIA TUBERCULOSIS BACTERIA Antibiotics Antibiotics drugs First antibiotics isolated from fungi and bacteria Grown on petri plates Noticed that one specific microbe couldn t grow near another The major drugs used to treat bacterial infections antibiotics are antibacterial o A few work against some protozoa but mainly just bacteria o Not antiviral Many types are synthesized in labs as chemical derivatives of natural antibiotic o Would just alter it to see if they could make it work better Penicillin the First Antibiotic Isolated from the fungi Penicillium in 1930s by Alexander Fleming Purified and used as a drug in 1941 Impact of Antibiotics Wartime o Civil War o WWI o WWII 66 of all military deaths due to disease 54 of all military deaths due to disease 28 of military deaths due to disease Antimicrobial Agents and Therapy Properties of Antimicrobial Drugs The drug has to be toxic to the microorganism but harmless to the o selective toxicity patient o must be able to reach infected site o must remain active at infected site One it gets to infected site must remain active there o others see Table 12 1 Antibacterial Drug Target Sites Figure 12 2 General Modes of Action o Static Drugs Static effect drug inhibits growth replication of microbe immune system kills remaining microbes o Cidal Drugs cidal effect drug kills the microorganism often dose dependent Target Sites Specific Modes of Action 1 Cell Wall Disruption o Cell wall is the target for many different kinds of drugs o Most work by interfering with production of peptidoglycan o Work best on young actively growing cells These are the cells that are producing a lot of their cell wall o Examples Penicillin prevents protein crosslinks from forming Bacitracin prevents subunits from being transported exported outside of the cell Target Sites Specific Modes of Action Target Sites Specific Modes of Action 2 Cell Membrane Disruption Layer that controls all movement in and out of cells o If you mess up the membrane than the permeability is lost Molecules that want in leak out etc o Due to similarities between all membranes drugs tend to be more toxic to humans Because all living cell membranes for most part have same structure So occasionally have drugs that kill bacteria very well but can have toxic effects on our cell membrane o effective against all age cells and relatively inactive cells Target Sites Specific Modes of Action Cell Membrane Disruption o Examples Antibacterial Drugs Polymixins Antiobiotics o disrupts membrane surface by interacting with phospholipids of Gram bacteria o Narrow spectrum Antifungal Drugs Both drugs interfere with sterols in cell membrane Polyenes Poly Most toxic to humans o form complexes with sterol lipids in fungal cell membranes abnormal openings o These are saved for very drastic cases because their so toxic Imidazoles o Inhibit sterol synthesis alter membrane permeability in fungal membranes o More Broadly Used o Less toxic to people have fewer side effects o Ex Antifungal sprays reproductive tract fungi Target Sites Specific Modes of Action Antimicrobial Drugs Specific Modes of Action 3 Inhibiting Nucleic Acids DNA RNA o Inhibit the unwinding of DNA molecule bacteria must unwind DNA molecule for replication and transcription Drugs block bacterial enzymes used in unwinding DNA gyrases These drugs keep enzyme from doing its job Example Quinolones o Inhibit RNA Polymerase Enzyme that makes RNA Example Rifampin Used for people with tuberculosis Antimicrobial Drugs Specific Modes of Action 4 Protein Synthesis Disruption o Drugs act on the mRNA ribosome complex o Drugs which bind to 30s subunit Aminoglycosides cause misreading of the mRNA Work by making bacterial cell sticking to a very specific place on a subunit Once there it throws off reading of genetic code Tetracyclines block attachment of tRNAs Stick to small subunit Keeps transfer RNA from coming in No proteins are synthesized o Drugs which bind to 50s subunit Chloramphenicol prevents peptide bond formation Binds to big subunits Then interferes with how the amino acid is linked together Erythromycin a macrolide prevents movement of ribosome along mRNA proteins Without proteins cell quickly dies Ribosomes make the Antimicrobial Drugs Specific Modes of Action 5 Disruption of Metabolic Pathways o Inhibit synthesis of nitrogenous bases o Drugs that interfere with some chemical reaction in the cell Folic acid an essential compound in the synthesis of nitrogenous bases AKA Folic Acid Inhibitors Drugs interfere with the production of folic acid o Folic acid is essential in the synthesis of