antibacterial Flashcards
MOA of B-lactams
inhibiting the synthesis of the peptidoglycan, layer of bacterial cell walls
To treat gram positive and negative bacteria
MOAR of B-lactams
- decreased membrane wall permeability
- Antibiotic unable to penetrate the outer membrane of Gram-negative bacteria
e. g. benzyl-penicillin
- Changes in permeability (membrane composition)
e.g., carbenicillin - Enzymatic inactivation of antibiotic
β-LACTAMS – expression / induction of β-lactamases
These enzymes are liberated extracellularly and hydrolyse the β-lactam ring
Gram-negative produce β –lactamases within their cell membrane (periplasmic space) (usually chromosomally encoded)
MOA of GLYCOPETIDES - vancomycin and teicoplanin
Inhibition of peptidoglycan synthesis by inhibiting transglucosylase which produces linear strands of peptidoglycan.
Prevent the transfer and addition of muramyl- pentapeptide building blocks.
they are gram positive and bactericidal
MOAR of Glycopeptidase
modification of target site
Biosynthesis of peptidoglycan with altered glycopeptide recognition sites –binding of glycopeptides is reduced.
MOA of tetracycline
Tetracycline binds to a single site in the 30S ribosomal subunit.
when it binds to it will prevent tuna from binding
MOAR of tetracyclines
Increased efflux
* Overexpression of norA in S. aureus (clinically significant resistance)
Modification of target site
Ribosomal protection factors; dislodging tetracycline from the ribosome (tetM (streptococci), tetO (Campylobacter jejuni)
MOA - MLS
macrolides
lincosamide
streptogramins
MLS selectively inhibit protein synthesis by binding the 50S subunit.
MLS are bacteriostatic.
“bacteriostatic” means that the agent prevents the growth of bacteria (i.e., it keeps them in the stationary phase of growth).
macrolides
binding of macrolides causes dissociation of peptidyl-tRNA from ribosomes.s
block translocation, causing the release of an incomplete polypeptides from the ribosome.
streptograms
are bacteriostatic when used individually but bactericidal when Quinupristin/Dalfopristin are used together
“bactericidal” means that it kills bacteria.
MOAR of MLS
- Enzymatic inactivation of antibiotic
* Hydrolysis of the lactone ring by plasmid encoded esterases (ereA and ereB)
* Inactivation of erythromycin and oleandomycin in enterobacteria (gram negative bacteria) - Modification of target site
Loss of macrolides binding to the ribosome (plasmid/transposon mediated)
MOA of AGACs
Gentamicin (aminoglycoside antibiotic)
Binds irreversibly to 30S ribosomal subunit. Stop translocation and stop protein synthesis.
May also
generate errors in the translation of the genetic code. affect bacterial membrane permeability.
Spectinomycin (aminocyclitol antibiotic)
binds to the 30S ribosomal subunit and in
hibit protein synthesis.
Bactericidal activity against some Gram-positive and many Gram-negative bacteria.
MOAR of AGAAs
Expression of acetyltransferases (AAC)
Expression of nucleotidyltransferases or adenyltransferases (ANT)
Expression of phosphotransferases (APH)
Modification of target site
Single step mutations in ribosomal proteins
other chloramphenicol , linezolid and mupirocin
Chloramphenicol binds 50S ribosomal subunit and prevents attachment of tRNA to its acceptor site, thus preventing peptide bond formation
- Bacteriostatic
Linezolid (oxazolidinone) binds 50S ribosomal sub-unit to block initiation phase of translation.
Mupirocin inhibits bacterial isoleucyl tRNA synthetase. (Prior to incorporation into polypeptides, amino acids are attached to specific tRNA molecules.)
other chloramphenicol , linezolid and mupirocin MOAR
Enzymatic inactivation of antibiotic
CHLORAMPHENICOL
* Chloramphenicol acetyltransferases (CATs) * ACTS: plasmid/transposon-encoded
2-mechanism of antibiotic resistance:
Modification of target site
FUSIDIC ACID
Protection of target; modified translocation factor protein with lowered affinity for antibiotic.
3-mechanism of antibiotic resistance of MUPIROCIN: Modification of target site
Duplication of target site (isoleucyl-tRNA synthetase, IRS) - plasmid-encoded
high-level resistance S. aureus (2nd version resistant)
4-mechanism of antibiotic resistance of CHLORAMPHENICOL:
Increased efflux
Overexpression of craA: major facilitator superfamily efflux pump in Acinetobacter
baumannii.
MOA of quinolones
WORKS BY INHIBITION OF DNA REPLICATION BY TARGETING DNA GYRASE.
Do not bind directly to either the gyrase A or B subunits, or to the intact enzyme
(A2B2).
Gyrase stimulates the binding of quinolones to dsDNA.
Gyrase cleaves dsDNA to produce exposed single- stranded regions that constitute binding sites for the antibiotics.
Key step in quinolone action is the trapping gyrase or topoisomerase IV on DNA as tertiary drug-enzyme-DNA complexes.
Quinolones stabilized the-stranded break in DNA created by gyrase so that re-ligation becomes unfavourable.
