Mechanisms of Antimicrobial Resistance Flashcards
Intrinsic Antibiotic Resistance
Resistance that happens as a natural property of the bacteria
Acquired Resistance
Genetic mutation or acquisition of new genes
Three Broad catagories of atbx resistance
Inactivate/modify drug
Alter the atbx target
Reduce the ability of drug to get to the target
Porins
Found in Gram (-) bacteria in their outer membrane, forming hydrophillic channels to taken in nutrients. Atbx can get in this way
Efflux Pumps
Structures in bacerial ccell membrane aimed to remove substrates from the cytoplasm
Gram - and +
B-lactams inhibit cell wall synthesis by
Binding to penicillin binding proteins that are responsible for peptide crosslinking in the peptidoglycan wall
B-Lactam resistance
Altering the drug: B-lactamase
Mod the target: altered PBPs
Narrow Spectrum B-lactamases
Bugs
Staphylococci, E. coli, H influenzae, klebsiella penumoniae
Narrow Spectrum B-lactamases
Only targets penicillin drugs
Found in both grams
ESBLs
Bugs
Just gram (-) rods
E. coli
Klebsiella pneumoniae
ESBLs
Can also target cephalosporins\
Plasmids usually
ampCs
Bugs
Enterobacter, pseudonomas
ampCs
Targets penicillins and 1-3 gen cephalosporins
Carbapenemases
Plasmid mediated
Mostly klebsiella, but can transfer to e. coli
KPC
Klebsella pneumoniae carbapenemases
Plasmid mediated
NDM-1
produced by klebsiella, hydrolzes all b-lactams
Plasmid mediated
Describe the regulation of ampC expression
Chromosomal, can be induced or constitutive
Some B-lactams can induce the production of ampC (ampicillin and cefazolin (ceph gen 1))
mecA
Altered PBP found in staphylococci
Encodes PBP2
Found in MRSA
Mosaic PBP
Found in S. pneumoniae and N. gonorrhoaea
Mosaid DNA strands coding for PBPs
Vancomycin
MoA
Binds to terminal D-ala-D-ala portion of the peptide chain precursor
Vancomycin
Resistance-modifying the target
Elmost exclusively enterococcus spp
Replaces the last alanine with a lactate, reducing binding affinity
Plasmia mediated
Vanco
Resistance- preventing drug-target interaction
S. aureus
Binding free vanco in the existing cell wall
VISA
Vancomycin intermediate susceptibility S. aureus
Thicker walls, with less cross linkingg
Quinolones
MoA
Target DNA gyrase and DNA topoisomerase
In gram negative bacteria, _____ is the more susceptible target of quinolones
DNA Gyrase
In gram positive bacteria, _____ is the more susceptible target of quinolones
Topoisomerase IV
Cipro targets
Gram negative and DNA gyrase
Levofloxacin targets
Both, but Topoisomerase IV better
Quinolone resistance
modding the target
DNA substitutions in both cell targets, called the quinolone-resistance-determining region (QRDR)
Macrolides
MoA
Binding to 50s subunit of ribosome
Macrolide Resistance
Modding the target
Methylating the ribosome, which also resists clindamycin
Constitutive or inducible (not ind to clinda though)
Macrolide Resistance
Efflux pumps
Resistant to macros, sensitive to clinda
Aminoglycoside Resistance
Modding the drug
N-acetylation
O-nucleotidylation
O-phosphorylation
Of the drug
Found on chromosome