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
– –
surfaces (e.g operating rooms) not totally effective
• ultra-violet light
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 undecaprenol
sugar amino acid
Cell wall
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 C
S NH
CH O
C
CH N
CH3 C CH
CH3 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