DR. MABANAG - BETA LACTAMS + OTHER CELL WALL & MEMBRANE ACTIVE ANTIBIOTICS Flashcards
4 Major categories of Bacterial targets
- Cell Wall
● Beta lactams, Vancomycin - Outer cell membrane
● Polymyxins - Nucleic acid
● Fluoroquinolone, Trimethoprim - Ribosomes
● Aminoglycosides, Spectinomycin, Tetracyclines, Macrolides, Chloramphenicol, Linezolid
○ Buy AT 30
- Aminoglycoside
- Tetracycline
○ SCEL at 50
- Streptogramins
- Chloramphenicol, Clindamycin
- Erythromycin (Macrolides)
- Linezolid
● There are two subfamilies:
○ Those that attack 50S Subunit
○ Attack 30S Subunit
● Antibiotics also attack Nucleic acid synthesis, like in
folate synthesis
C-S-T
cotrimoxazole
sulfonamides
trimethoprim
attack the DNA gyrase.
QUINOLONES
attacks the RNA polymerase.
RIFAMPIN
______bactericidal by inhibiting bacterial cell wall synthesis leading to loss of cell wall integrity and eventually cell lysis
BETA LACTAMS
most complex subclasses of beta-lactams
P-C
PENICILLIN
CEPHALOSPORINS
All beta-lactams inhibit synthesis of the ___________found on the bacterial cell wall
PEPTIDOGLYCAN LAYER
● A heteropolymer component of bacterial cell wall that provides rigid mechanical stability
● It maintains bacterial cell shape and integrity and prevents bacterial cell lysis from high osmotic pressure.
PEPTIDOGLYCAN LAYER
PEPTIDOGLYCAN LAYER
Composed of alternating chains of:
?
?
○ N-acetylglucosamine (NAG)
○ N-acetylmuramic acid (NAM)
● They are pentaglycine cross-linked by peptide
chains
● If peptidoglycan is weakened or synthesis is inhibited, cell lysis occurs or the cell would not be able to replicate.
PEPTIDOGLYCAN LAYER COMPOSITION
OLD BETA LACTAMS ARE MORE ACTIVE AGAINST GRAM + THAN GRAM-
○ Gram-positive = Very thick peptidoglycan layer
○ Gram-negative = Thin peptidoglycan layer
inhibit synthesis of the peptidoglycan layer by binding to and inhibiting the action of TRANSPEPTIDASE involved in the cross-linking of peptidoglycan chains.
ALL BETA-LACTAMS
○ Involved in the cross-linking of
peptidoglycan chains
○ It represents one of the multiple types of
penicillin-binding proteins (PBPs).
○ Inhibitory action on the transpeptidase
enzyme has a bactericidal effect as the impaired peptidoglycan synthesis leads to loss of bacterial shape and integrity thus leading to cell lysis and cell death.
TRANSPEPTIDASE
- Porin Mutations (e.g., Klebsiella spp.)
● Decreases entry of beta-lactams. - Action of B-Lactamases
● Degradation of antibiotics once inside the cell.
● Combat against antibiotics. - Efflux Pumps (e.g., P. aeruginosa)
● Removal of antibiotic once inside the cell. - PBP mutations
● Not allowing binding of beta-lactam.
● So that the drug cannot attach.
Major mechanisms of beta-lactam resistance:
Resistance for beta-lactams in G(-) bacilli are usually due to
BETA LACTAMASE PRODUCTION
encode plasmids (which are passed from bacterium to bacterium by horizontal transfer) or encoded by the bacterial chromosome itself.
Beta-lactamases (anti-beta lactam enzymes)
BETA LACTAMASE:
Inactivate penicillins
Penicillinases
