Dr. Alvin Fox

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Antibiotics cell envelope,Lecture 28
Dr. Alvin Fox
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Key Words
Sterilization/disinfection/antisepsis Beta
lactam Antibiotic Penicillins Selective
toxicity Cephalosporins/cephamycins Bacte
ricidal 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
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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
• being replaced e.g. H2O2/free radicals
• ultra-violet light
• surfaces (e.g. operating rooms)
• not totally effective
• gamma radiation
• mainly food industry

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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)
• minimize harm to patient

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Antibiotics

• damage structures
• present in bacteria
• not present in host

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Antibiotics work together with the 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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Cross-linking of peptidoglycan
Old
New
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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
L-ala to D-ala - inhibits formation of
D-ala-D-ala
Cytoplasm
X
X
sugar
amino acid
X
X
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Bacitracin

• Inhibits dephosphorylation

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TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE
Cell membrane
Cell wall
undecaprenol
P
P
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TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE
Cell wall
Cell membrane
undecaprenol
P
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TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE
Cell wall
Cell membrane
undecaprenol
P P
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TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE
Cell wall
Cell membrane
undecaprenol
P P
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TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE
Cell membrane
Cell wall
undecaprenol
P
P
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MINUS BACITRACIN
TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS
MEMBRANE
Cell wall
Cell membrane
undecaprenol
P
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PLUS Bacitracin
TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS
MEMBRANE
Cell wall
Cell membrane
undecaprenol
P P
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Vancomycin
Cell wall
Vancomycin

• binds to D-ala-D-ala
• inhibits cross-linking

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Beta lactam antibiotics

• penicillins
• cephalosporins/cephamycins
• monobactams

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ß lactams
Cell wall

• inhibit penicillin binding proteins
• stop cross-linking

ß lactam
Active site of enzyme
Penicillin binding protein
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STRUCTURE OF PENICILLIN
Site of penicillinase action. Breakage of the ß
lactam ring.
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Attached to lactam ring

• penicillins
• 5 membered ring
• Cephalosporins/cephamycins
• 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 ß lactamase (penicillinase)
• destroys antibiotic
• modified penicillin binding proteins
• dont bind antibiotic
• modified porins
• no internalization of antibiotic

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Clavulinic acid

• ß lactam
• binds strongly to ß lactamases
• inhibits activity
• limited potency as antibiotic
• used in conjunction with other ß lactams

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Polymyxin B

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

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Daptomycin

• Causes depolarization of bacterial cell
  membrane

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Anti-tuberculosis drugs

• Isoniazid and Ethionamide
• - chemically related
• - blocks mycolic acid synthesis
• Ethambutol
• blocks arabinogalactan synthesis
• Cycloserine