抗生素与细胞膜（英文ppt）antibiotics and cell envelope课件

1 Dr. Alvin Fox Antibiotics: cell envelope, Lecture 36 2 Key WordsKey Words Sterilization/disinfection/antisepsis Beta lactam Antibiotic Penicillins Selective toxicity Cephalosporins/cephamycins Bactericidal Monobactam Bacteriostatic Clavulinic acid Minimal inhibitory concentration (MIC) Penicillinase/beta lactamase Susceptibility testing Polymyxin B Penicillin binding proteins Daptomycin Autolysins Isoniazid Cycloserine Ethioniamide Bacitracin Ethambutol Vancomycin Resistance 3 STERILIZATIONSTERILIZATION All killed All killed non-selective non-selective 4 SterilizationSterilization autoclavingautoclaving 121121 o o C (heat/pressure)C (heat/pressure) * * Heat resistant materialsHeat resistant materials ethylene oxideethylene oxide non heat resistantnon heat resistant Usually equipment Usually equipment being replaced e.g. Hbeing replaced e.g. H 2 2O O2 2 /free radicals/free radicals ultra-violet lightultra-violet light surfaces (e.g. operating rooms)surfaces (e.g. operating rooms) not totally effectivenot totally effective gamma radiationgamma radiation mainly food industry mainly food industry 5 Membrane filters porespores bacteriabacteria 6 DisinfectionDisinfection Liquids that kill bacteriaLiquids that kill bacteria e.g. phenol basede.g. phenol based too toxic for skin surfacestoo toxic for skin surfaces 7 AntisepticsAntiseptics Topical (e.g. skin) Topical (e.g. skin) e.g. iodine or 70% alcohol e.g. iodine or 70% alcohol “reduce” bacterial load “reduce” bacterial load 8 ANTIBIOTICSANTIBIOTICS Selectively toxic for bacteriaSelectively toxic for bacteria bactericidal (killing) bactericidal (killing) bacteriostatic (growth inhibition) bacteriostatic (growth inhibition) minimize harm to patient minimize harm to patient 9 AntibioticsAntibiotics destroy structuresdestroy structures present in bacteriapresent in bacteria not present in hostnot present in host 10 Antibiotics work togetherAntibiotics work together with with the immune the immune systemsystem 11 Minimal inhibitory Minimal inhibitory concentrationconcentration lowest level stopping growthlowest level stopping growth e. g. zone of inhibition around a disk e. g. zone of inhibition around a disk impregnated with antibioticimpregnated with antibiotic 12 Antibiotics that inhibit cell wall Antibiotics that inhibit cell wall biosynthesis are bactericidalbiosynthesis are bactericidal Without cell wall, osmotic pressure Without cell wall, osmotic pressure causes bacteria to burstcauses bacteria to burst 13 Cross-linking of peptidoglycan Old New 14 Peptidoglycan synthesisPeptidoglycan synthesis CytoplasmCytoplasm Cell wallCell wall undecaprenolundecaprenol sugarsugar aminoamino acidacid Cell MembraneCell Membrane 15 CycloserineCycloserine X X CytoplasmCytoplasm sugarsugar aminoamino acidacid X X X X X X alanine (ala) analog alanine (ala) analog - inhibits conversion L-ala to D-ala - inhibits conversion L-ala to D-ala - inhibits formation of D-ala-D-ala - inhibits formation of D-ala-D-ala 16 BacitracinBacitracin Inhibits dephosphorylationInhibits dephosphorylation 17 TRANSPORT OF TRANSPORT OF PEPTIGOGLYCAN SUBUNIT PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANEACROSS MEMBRANE Cell membraneCell membrane undecaprenolundecaprenol P P P P Cell wallCell wall 18 TRANSPORT OF TRANSPORT OF PEPTIGOGLYCAN SUBUNIT PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANEACROSS MEMBRANE Cell membraneCell membrane undecaprenolundecaprenol P P P P Cell wallCell wall 19 TRANSPORT OF TRANSPORT OF PEPTIGOGLYCAN SUBUNIT PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANEACROSS MEMBRANE Cell membraneCell membrane undecaprenolundecaprenol P P P P Cell wallCell wall 20 TRANSPORT OF TRANSPORT OF PEPTIGOGLYCAN SUBUNIT PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANEACROSS MEMBRANE Cell membraneCell membrane undecaprenolundecaprenol P P P P Cell wallCell wall 21 TRANSPORT OF TRANSPORT OF PEPTIGOGLYCAN SUBUNIT PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANEACROSS MEMBRANE Cell membraneCell membrane undecaprenolundecaprenol P P P P Cell wallCell wall 22MINUSMINUS BACITRACINBACITRACIN CellCell membranemembrane undecaprenolundecaprenol P P Cell wallCell wall TRANSPORT OF TRANSPORT OF PEPTIGOGLYCAN SUBUNIT PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANEACROSS MEMBRANE 23 PLUSPLUS BacitracinBacitracin Cell membraneCell membrane undecaprenolundecaprenol P P P P Cell wallCell wall TRANSPORT OF TRANSPORT OF PEPTIGOGLYCAN SUBUNIT PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANEACROSS MEMBRANE 24 VancomycinVancomycin Cell wallCell wall binds to D-ala-D-ala binds to D-ala-D-ala inhibits cross-linking inhibits cross-linking Vancomycin 25 Beta lactam antibioticsBeta lactam antibiotics penicillins penicillins Cephalosporins/cephamycins Cephalosporins/cephamycins monobactamsmonobactams 26 lactamslactams Cell wallCell wall Penicillin binding proteinPenicillin binding protein inhibit penicillin inhibit penicillin binding proteinsbinding proteins stop cross-linkingstop cross-linking lactam Active site of enzyme 27 CNHCHCHC O OCNCH CH3 CH3 COOH S Site of penicillinase action. Breakage of the lactam ring. STRUCTURE OF PENICILLIN 28 Attached to lactam ringAttached to lactam ring penicillins penicillins 5 membered ring 5 membered ring Cephalosporins/cephamycins Cephalosporins/cephamycins 6 membered ring6 membered ring monobactams monobactams no second ringno second ring 29 Chemical modifications change Chemical modifications change biological activitybiological activity Early lactam antibiotics Early lactam antibiotics inactive against Gram negative inactive against Gram negative bacteriabacteria no penetration of outer membraneno penetration of outer membrane 30 Resistance mechansimsResistance mechansims Produce Produce lactamase (penicillinase)lactamase (penicillinase) destroys antibioticdestroys antibiotic modified penicillin binding proteins modified penicillin binding proteins dont bind antibiotic dont bind antibiotic modified porinsmodified porins no internalization of antibioticno internalization of antibiotic 31 lactam lactam binds strongly to binds strongly to lacta