1、1,Dr. Alvin Fox,Antibiotics: cell envelope, Lecture 28,2,Key Words,Sterilization/disinfection/antisepsis Beta lactam Antibiotic Penicillins Selective toxicity Cephalosporins/cephamycins Bactericidal Monobactam Bacteriostatic Clavulinic acid Minimal inhibitory concentration (MIC) Penicillinase/beta l
2、actamase Susceptibility testing Polymyxin B Penicillin binding proteins Daptomycin Autolysins Isoniazid Cycloserine Ethioniamide Bacitracin Ethambutol Vancomycin Resistance,3,STERILIZATION,All killednon-selective,4,Sterilization,autoclaving 121oC (heat/pressure) Heat resistant materials ethylene oxi
3、de non heat resistantUsually equipment being replaced e.g. H2O2/free radicals ultra-violet light surfaces (e.g. operating rooms) not totally effective gamma radiationmainly food industry,5,Membrane filters,pores,bacteria,6,Disinfection,Liquids that kill bacteria e.g. phenol based too toxic for skin
4、surfaces,7,Antiseptics,Topical (e.g. skin) e.g. iodine or 70% alcohol “reduce” bacterial load,8,ANTIBIOTICS,Selectively toxic for bacteriabactericidal (killing) bacteriostatic (growth inhibition)minimize harm to patient,9,Antibiotics,damage structurespresent in bacterianot present in host,10,Antibio
5、tics work together with the immune system,11,Minimal inhibitory concentration,lowest level stopping growthe. g. zone of inhibition around a disk impregnated with antibiotic,12,Antibiotics that inhibit cell wall biosynthesis are bactericidalWithout cell wall, osmotic pressure causes bacteria to burst
6、,13,Cross-linking of peptidoglycan,Old,New,14,Peptidoglycan synthesis,Cytoplasm,Cell wall,undecaprenol,sugar,amino acid,Cell Membrane,15,Cycloserine,X,Cytoplasm,sugar,amino acid,X,X,X,alanine (ala) analog - inhibits conversion L-ala to D-ala - inhibits formation of D-ala-D-ala,16,Bacitracin,Inhibits
7、 dephosphorylation,17,TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE,Cell membrane,undecaprenol,P,P,Cell wall,18,TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE,Cell membrane,undecaprenol,P,Cell wall,19,TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE,Cell membrane,undecaprenol,P P,Cell wal
8、l,20,TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE,Cell membrane,undecaprenol,P P,Cell wall,21,TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE,Cell membrane,undecaprenol,P,P,Cell wall,22,MINUS BACITRACIN,Cell membrane,undecaprenol,P,Cell wall,TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRAN
9、E,23,PLUS Bacitracin,Cell membrane,undecaprenol,P P,Cell wall,TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE,24,Vancomycin,Cell wall,binds to D-ala-D-alainhibits cross-linking,Vancomycin,25,Beta lactam antibiotics,penicillins cephalosporins/cephamycins monobactams,26, lactams,Cell wall,Penicilli
10、n binding protein,inhibit penicillin binding proteinsstop cross-linking, lactam,Active site of enzyme,27,Site of penicillinase action. Breakage of the lactam ring.,STRUCTURE OF PENICILLIN,28,Attached to lactam ring,penicillins 5 membered ring Cephalosporins/cephamycins 6 membered ring monobactams no
11、 second ring,29,Chemical modifications change biological activity,Early lactam antibiotics inactive against Gram negative bacteria no penetration of outer membrane,30,Resistance mechansims,Produce lactamase (penicillinase) destroys antibiotic modified penicillin binding proteins dont bind antibiotic
12、 modified porins no internalization of antibiotic,31, lactam binds strongly to lactamases inhibits activitylimited potency as antibioticused in conjunction with other lactams,Clavulinic acid,32,Polymyxin B,bindslipid A phospholipidsdisrupts outer membrane, Gram negative bacteria toxic to human cells,33,Daptomycin,Causes depolarization of bacterial cell membrane,34,Isoniazid and Ethionamide - chemically related - blocks mycolic acid synthesisEthambutol blocks arabinogalactan synthesisCycloserine,Anti-tuberculosis drugs,
