antibacterials mechanisms of reistance Flashcards
what are common multi-drug resistant Gram negative pathogens
Klebsiella pneumonaie
Pseudomonas aeruginosa
E.coli
What are the types of antimicrobial resistance?
Intrinsic
Acquired (Genetic (irreversible) and Phenotypic (reversible)
How is drug resistance transferred between bacteria?
Conjugation
what are the three mechanisms of resistance?
Inactivate/modify drug
Alter drug target site
Alter drug uptake/exit
what are B lactamases?
Enzymes that break B lactam ring open, deactivating the molecule’s antibacterial activity
where does the B lactam accumulate in gram negative bacteria
it accumulates in the periplasmic space, gets stuck between the PG and outer membrane.
LIST three B lactamase inhibitors
Clavulanic acid (i.e co amoxiclav)
Sulbactam
Tazobactam
how does altered target site work for Beta lactams?
altered penicillin binding proteins through MeCA gen, which means the B lactam cant bind,
Gene mutation
What does altered uptake mean?
In gram negative bacteria, there will be reduced number and size of porins which decreases permeability and prevent uptake
How does resistance to vancomycin (glycopeptide) work? (altered target site?)
Van A resistance: change in terminal amino acids of peptide chain. D-ala-D-ala —> to D-ala-D-lactate
which leads to unstable complex and less H bonds
How does the resistance to Fluoroquinolones work? (altered target site)
Chromosomal mutations in DNA gyrase or Topoisomerase IV inhibit binding of antibiotic to its target
How does resistance to Tetracyclines work? (altered transport)
Expressed in both gram negative and positive bacteria
they actively pump substrates out of the bacteria cell
What are the two classes of efflux pump associated with AMR?
RND pumps expressed by gram negative bacteria
MFS pumps expressed by gram positive bacteria
