Microbiology Final Exam 5

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paul ehrlich

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developed concept of selective toxicity, identified dyes that effectively treated African Sleeping Sickness

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penicillin

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accidentally discovered by Alexander Fleming, Fleming, Florey, and Chainreceived nobel prize in 1945 for discovery and production of penicillin

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penicillin mode of action

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blocks the enzyme that catalyzes transpeptidation, prevents thesynthesis of complete cell walls leading to lysis of cell, acts only on growingbacteria that are synthesizing new peptidoglycan, most crucial feature of themolecule is the B lactam ring, essential for bioactivity, many penicillinresistant organisms produce Beta lactamase (penicillinase) which hydrolyzes abond in this ring

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resistance

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if bacteria contain penicillinases, clavulanicacid –inhibits beta lactamases, can be added to semysinthetic penicillinsto augment their effectiveness, ex. Augmentin– clavulanic acid + amoxicillin treat streptococci, meningococci, andspirochete infections

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cephalosporins produced by fungus cephalosporium

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same mode of action as penicillins, treats gonorrhea, broad spectrumantibiotics that can be used by most patients that are allergic to penicillin

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ability of drug to reach site of infection

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depends in part on mode of administration; oral – some drugs destroyedby stomach acid, topical; intravenous – nonoral routes of administration(intravenous, subcutaneous, intramuscular) drug can be excluded by blood cotsor necrotic tissue

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antimycobacterialantibiotics

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isoniazid (INH) inhibits mycolic acid synthesis ; Ethambutol – inhibits incorporationof mycolic acid into cell wall

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antimicrobial drugs

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1) inhibitors of cell wall synthesis, 2) protein synthesis inhibitors 3)metabolic antagonists – antimetabolites 4) nucleic acid synthesis inhibition

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Beta-Lactam Antibiotics

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penicillins and cephalosporins, one of the most important groups ofantibitoics of all time, penicillins, cephalosporins, target cell wallsynthesis

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protein synthesis inhibitors

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many antibiotics bind specifically to the bacteria ribosome, otherantibiotics inhibit a step in protein synthesis

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Aminoglycosideantibiotics

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large family which all contain a cyclohexane ring and amino sugars, bindto 30S ribosomal subunit and interfere with protein synthesis by directlyinhibiting the process and by causing misreading of the messenger RNA,resistance and toxicity, antibiotics that contain amino sugars bonded byglycosidic linkage, ex. Kanamycin, streptomycin

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tetracyclines

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sometimes used to treat acne, broad spectrum

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macrolides

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contain lactone rings bonded to sugars, ex. Erythromycin, broad spectrum antibiotic that targets the 50S subunit of ribosome, used for patients allergic to penicillin

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platensimycin

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new structural class of antibiotic Broad-spectrum, effective againstMRSA and vancomycin-resistant enterococci

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chloramphenicol

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bone marrow toxicity, aplastic anemia in developing countries, toxicwith numerous side effects so only used in life threatening situations

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metabolic antagonists

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act as antimtabolites, antagonizeor block functioning of metabolic pathways by competitively inhibiting the useof metabolites by key enzymes, structural analogs

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Sulfonamides or SulfaDrugs

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sulfa drugs are selectively toxicfor these pathogens because they compete with PABA for the active site of anenzyme involved in folic acid synthesis, resulting in a decline in folic acidconcentration, pathogen dies because folic acid is a precursor to purines andpyrimidines which are nucleic building blocks

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nucleic acid synthesis inhibition

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drugs not as selectively toxic as other antibiotics because bacteriaand eukaryotes do not differ greatly in the way they synthesize nucleic acids

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quinolones

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inhibition of topoisomerase IV is thought to interfere with separationof replicated chromosomal DNA, Inhibition of DNA gyrase blocks relaxtion ofsupercoild DNA,relaxation being a requirement for transcription and replication

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antiviral drugs

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neuraminidase inhibitors (limit influenza infection ) tamiflu

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drug resistance

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microbes in abscesses or biofilms may be growing slowly and not besusceptible “Superbug” a methicillin-resistant Staphylococcus aureus (MRSA)that developed resistance to vancomycin, this new vancomycin resistant S. aures(VRSA) was also resistant to most other antibiotics, isolated from foot uclerson a diabetic patient, acquired from conjugation with vancomyocin resistantenterococci (VRE) were isolated from same patient

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mechanisms of drug resistance

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prevent entrance of drug, drug efflux, inactivation of drug,modification of target enzyme or organelle, use of alternative pathwyas orincreased production of target metabolite

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the origin and transmission of drug resistance

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immunity genes, horizontal gene transfers, chromosomal genes, R plasmids

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overcoming drug resistance

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give drug in appropriate concentrations to destroy susceptible, give twoor more drugs at same time, use drugs only when necessary, possible futuresolutions: continued development of new drugs, use of bacteriophages to treatbacterial disease