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Antibiotics that affect the Cell Envelope
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Key Words Sterilization/disinfection/antisepsis Bacitracin
Antibiotic Vancomycin Selective toxicity beta lactam Bactericidal Penicillins Bacteriostatic Cephalosporins Minimal inhibitory concentration (MIC) Monobactam Susceptibility testing Clavulinic acid Penicillin binding proteins Penicillinase/beta lactamase Autolysins Polymyxin B Cycloserine Resistance
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STERILIZATION All killed non-selective
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Sterilization autoclaving ethylene oxide ultra-violet light
121oC (heat/pressure) Heat resistant materials ethylene oxide Non heat resistant usually equipment ultra-violet light surfaces (e.g operating rooms) not totally effective
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Membrane filters pores bacteria
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Disinfection Liquids that kill bacteria e.g. phenol based
too toxic for skin surfaces
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Antiseptics Topical (e.g. skin) e.g. iodine or 70% alcohol
“reduce” bacterial load
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ANTIBIOTICS Selectively toxic for bacteria bactericidal (killing)
bacteriostatic (growth inhibition) no harm to patient
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Antibiotics destroy structures present in bacteria not present in host
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Antibiotics work together
with immune system
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Minimal inhibitory concentration
lowest level stopping growth e. g. zone of inhibition around a disk impregnated with antibiotic
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Antibiotics that inhibit cell wall
biosynthesis are bactericidal Without cell wall, osmotic pressure causes bacteria to burst
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Peptidoglycan synthesis
Cytoplasm Cell Membrane Cell wall undecaprenol sugar amino acid
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Cycloserine alanine (ala) analog inhibits conversion of L-ala to D-ala
inhibits formation of D-ala-D-ala
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Cycloserine Analog of alanine Cytoplasm X X sugar amino acid X X
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Bacitracin Inhibits dephosphorylation
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Bacitracin Cell membrane undecaprenol P P
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Vancomycin binds to D-ala-D-ala inhibits cross-linking
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Vancomycin Cell wall
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Beta lactam antibiotics
penicillins cephalosporins monobactams inhibit penicillin binding proteins stop cross-linking
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Beta lactams Cell wall Penicillin binding protein
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Cross-linking of peptidoglycan
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STRUCTURE OF PENICILLIN
NH CH O N CH3 COOH S Site of penicillinase action. Breakage of the lactam ring.
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Attached to lactam ring
penicillins 5 membered ring cephalosporins 6 membered ring monobactams no second ring
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Chemical modifications change biological activity
Early lactam antibiotics inactive against Gram negative bacteria no penetration of outer membrane
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Resistance mechansims
Produce beta lactamase (penicillinase) destroys antibiotic modified penicillin binding proteins don’t bind antibiotic modified porins no internalization of antibiotic
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Clavulinic acid beta lactam binds strongly beta lactamases
inhibits activity
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Polymyxin B lipid A phospholipids
binds lipid A phospholipids disrupts outer membrane, Gram negative bacteria toxic to human cells
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