Antibiotics that affect the Cell Envelope

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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 Bacteriostat
ic
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
• 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
Cell Membrane
Cytoplasm
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
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
• dont 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

• binds
• lipid A
• phospholipids
• disrupts outer membrane, Gram negative bacteria
• toxic to human cells