Faculty: Dr.

Alvin Fox
 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
STERILIZATION

• All killed
• non-selective
 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
 Membrane filters

pores

bacteria
 Disinfection
• Liquids that kill bacteria
– e.g. phenol based
– too toxic for skin surfaces
 Antiseptics
• Topical (e.g. skin)
– e.g. iodine or 70% alcohol
– “reduce” bacterial load
 ANTIBIOTICS
• Selectively toxic for bacteria
– bactericidal (killing)
– bacteriostatic (growth inhibition)

• no harm to patient
 Antibiotics
• destroy structures
– present in bacteria
– not present in host
Antibiotics work together
with immune system
 Minimal inhibitory
concentration

• lowest level stopping growth

• e. g. zone of inhibition around a disk

impregnated with antibiotic
• Antibiotics that inhibit cell wall
biosynthesis are bactericidal

• Without cell wall, osmotic pressure

causes bacteria to burst
 Peptidoglycan synthesis
Cytoplasm Cell Membrane Cell wall

undecaprenol

sugar

amino
acid
 Cycloserine

– alanine (ala) analog

– inhibits conversion of L-ala to D-ala
– inhibits formation of D-ala-D-ala
 Cycloserine
Analog of alanine
Cytoplasm

X X
sugar

amino
acid

X
X
 Bacitracin
• Inhibits dephosphorylation
Bacitracin

Cell membrane
undecaprenol

P
P
 Vancomycin
• binds to D-ala-D-ala
• inhibits cross-linking
Vancomycin
Cell wall
 Beta lactam antibiotics
• penicillins
• cephalosporins
• monobactams

• inhibit penicillin binding proteins

• stop cross-linking
Beta lactams
Cell wall

Penicillin binding protein

Cross-linking of peptidoglycan
STRUCTURE OF PENICILLIN

O
S
CH3
C NH CH CH C
CH3
O C N CH COOH

Site of penicillinase action.

Breakage of the  lactam ring.
 Attached to lactam ring
• penicillins
– 5 membered ring
• cephalosporins
– 6 membered ring
• monobactams
– no second ring
Chemical modifications change
biological activity
• Early lactam antibiotics
– inactive against Gram negative
bacteria
• no penetration of outer membrane
 Resistance mechansims
• Produce beta lactamase (penicillinase)
– destroys antibiotic
• modified penicillin binding proteins
– don’t bind antibiotic
• modified porins
– no internalization of antibiotic
 Clavulinic acid

• beta lactam

• binds strongly beta lactamases

– inhibits activity
 Polymyxin B
• binds
– lipid A
– phospholipids

• disrupts outer membrane, Gram negative bacteria

• toxic to human cells