Mechanisms of Antimicrobial Resistance Flashcards
The enzymes that perform cross-linking of peptidoglycan are called _____.
penicillin binding proteins (PBPs)
How does S. aureus prevent target-drug interaction in vancomycin resistance?
free vancomycin is bound in the existing peptidoglycan cell wall
What are efflux pumps?
structures in bacterial cell membranes that eliminate certain substances, incl. abx
How do bacteria prevent target-drug interaction in vancomycin resistance?
free vancomycin is bound in the existing peptidoglycan cell wall
The peptidoglycan precursor ends in _____.
2 D-alanines
_____ are β-lactam antibiotics with the broadest spectrum of activity against most gram - rods.
Carbapenems
Name 2 broad ways bacteria can become resistant to vancomycin.
- modifying the target 2. preventing target-drug interaction
_____ are structures in bacterial cell membranes that eliminate certain substances, incl. abx.
Efflux pumps
What does PBP stand for?
penicillin-binding proteins
Which drug induces erm?
macrolides
ESBLs are mostly found in ____, exclusively in _____.
plasmids; gram - rods
What are β-lactamases?
enzymes that inactivate β-lactam Abx by splitting the amide bond
What is the tx for species that express ampC?
carbapenems
How does Enterococcus spp become vanc resistant?
it changes the 5 member peptide that hangs off MurNAc so vancomycin cant recognize it
If erm is constitutively expressed, the bacteria will be resistant to _____. If erm is inducably expressed, the bacteria will be resistant to _____.
macrolides and clindamycin; macrolides only
Carbapenemases causing the most problems are plasmid-mediated and are found mainly in some _____ isolates, although transfer to ____ has occurred.
Klebsiella pneumoniae; E. coli
Give an example of intrinsic resistance.
vancomycin resistance of gram- organisms b/c it can’t penetrate the outer membrane
Where are porins found?
in the outer membrane of gram - bacteria
What is intrinsic resistance?
occurs just because via natural properties of the bacteria
β-lactamases are found in both gram + and gram - bacteria, but the worse ones are in the _____.
gram -
What is KPC?
Klebsiella pneumoniae carbapenemase- hydrolyzes all carbapenems and all other β-lactams
____ targets DNA gyrase as well as Cipro but also targets topo IV.
Levofloxacin
Carbapenemases causing the most problems are ____ and are found mainly in some Klebsiella pneumoniae isolates, although transfer to E. coli has occurred.
plasmid-mediated
What is mecA?
gene staph has that encodes a different PBP- causes MRSA
What does ESBL stand for?
extended spectrum beta-lactamases
Efflux pumps are found in _____ and _____ bacteria.
gram -, gram +
Anaerobic bacteria are inherently resistant to _____.
aminoglycosides
What do porins do?
form hydrophilic channels to allow selective uptake of nutrients, including some Abx
What is the D test?
distinguishes between erm and efflux-based resistance in bacteria; erm = D shape colony growth
____ is much for effective for gram negative bacteria than gram positives.
Cipro
During peptidoglycan cross linking, a ____ is cleaved
D-alanine
PBPs perform _____ and/or _____ reactions.
transpeptidase; transglycosylase
How are mecA staph treated?
5th gen cephalosporin
Carbapenems are β-lactam antibiotics with the broadest spectrum of activity against most ____.
gram - rods
_____ causing the most problems are plasmid-mediated and are found mainly in some Klebsiella pneumoniae isolates, although transfer to E. coli has occurred.
Carbapenemases
What does ampC encode? Why is it unique?
a β-lactamse that can hydrolyze penicillins, cephalosporins, and is not inhibited by beta-lactamase inhibitors
Where is ampC found?
the chromosome of gram - rods (Enterobacter, Pseudomonas)
Cipro is much more effective against _____ bacteria than _____ ones.
gram negative; gram positive
Name 2 ways bacteria become resistant to macrolides.
- methylate the 23s ribosome via erm gene 2. prevent drug-drug interaction via efflux pumps
______ act by irreversibly binding and inactivating the transpeptidase reaction of PBPs, thereby inhibiting peptide cross-linking and peptidoglycan synthesis.
β-lactam antibiotics
Where are the β-lactamase genes located?
on chromosomes (Klebsiella pneumoniae) or on plasmids (Staph. aureus, E. coli, H. influenzae)
Where is the erm gene found?
on transposons or plasmids
Name 3 ways bacteria become resistant to β-lactam antibiotics.
- modify the drug (enzymatic destruction) 2. modify the target (alter the PBPs) 3. prevent drug-target interaction (porins and efflux mechanisms)
_____ occurs just because, via natural properties of the bacteria.
Intrinsic resistance
ampC expression is either ____ or _____.
inducible, constitutive
β-lactam antibiotics act by irreversibly binding and inactivating the transpeptidase reaction of PBPs, thereby inhibiting ____ and _____.
peptide cross-linking; peptidoglycan synthesis
____ is due to genetic mutations or acquisition of new genes (plasmids, bacteriophages, transposons).
Acquired resistance
What are the 3 major mechanisms of resistance?
- inactivation/modification of the drug 2. altered antibacterial target 3. reduced drug delivery to the target
______ is formed by the addition of subunits called precursors (GlcNAc-MurNAc with 5 aas on the MurNAc).
Peptidoglycan
____ targets topo IV preferentially; it’s best against gram positives but still has some gram negative activity, but NOT against Pseudomonas.
Moxifloxacin
How do bacteria modify the target in vancomycin resistance?
change the 5 member peptide that hangs off MurNAc so vancomycin cant recognize it
_____ has good gram negative activity and much improved gram positive activity.
Levofloxacin
Peptidoglycan is formed by the addition of subunits called precursors (_____ with 5 aas on the _____).
GlcNAc-MurNAc; MurNAc
How do macrolides work?
bind to the 23s portion of the 50s ribosome to inhibit peptide chain elongation
What do narrow spectrum β-lactamases do?
hydrolize penicillin-type Abx
What do the vanA and vanB genes in VRE do?
change the peptide chain from D-ala, D-ala to D-ala, D-lactate
β-lactam antibiotics act by irreversibly binding and inactivating the _____ reaction of PBPs, thereby inhibiting peptide cross-linking and peptidoglycan synthesis.
transpeptidase
Cipro preferentially targets ____ over ____.
DNA gyrase; topo IV
What genes do VRE have that encode their vanc resistance? Where are they located?
vanA and van B; plasmids
____ perform transpeptidase and/or transglycosylase reactions.
PBPs
Which bacteria changes the 5 member peptide that hangs off MurNAc so vancomycin cant recognize it?
enterococcus (VRE)
Which bugs have mosaic PBPs?
Strep. pneumonia and N. gonorrhoeae
Where is NDM-1 found?
on plasmids
What is acquired resistance?
genetic mutation or acquisition of new genes (plasmids, bacteriophages, transposons)
Changes in porins or efflux pumps may cause ____.
changed uptake of Abx
Where is KPC found?
on plasmids
Levofloxacin targets DNA gyrase as well as Cipro but also targets ____.
topo IV
How can bacteria become resistant to fluoroquinolones?
change amino acids in DNA gyrase and topo; drug efflux
Moxifloxacin targets _____ preferentially; it’s best against gram positives but still has some gram negative activity, but NOT against Pseudomonas.
topo IV
_____ are inherently resistant to aminoglycosides.
Anaerobic bacteria
DNA gyrase is targeted by quinolones in _____ bacteria; topo IV is targeted by them in _____.
gram (-); gram (+)
Methylation of the ribosome confers resistance to ____ and ____ Abx.
macrolides; clindamycin
Carbapenems are _____ with the broadest spectrum of activity against most gram - rods.
β-lactam antibiotics
Extended spectrum beta-lactamases (ESBLs) are notable bc they can attack most ___.
cephalosporins
What is NDM-1?
enzyme that hydrolyzes all β-lactams except aztreonam
Levofloxacin has good ____ activity and much improved _____ activity.
gram negative; gram positive
What does a carbapenem treat?
gram - rods
_____ preferentially targets DNA gyrase over topo IV.
Cipro
How are mosaic PBPs formed?
by picking up naked DNA from the environment and swapping them for similar pieces of their own PBP DNA
Peptidoglycan is formed by the addition of subunits called _____ (GlcNAc-MurNAc with 5 aas on the MurNAc).
precursors
What are penicillin binding proteins (PBPs)?
enzymes that cross-link peptidoglycan
Which bacteria binds free vancomycin up in the cell wall, preventing its action?
S. aureus
Moxifloxacin targets topo IV preferentially; it’s best against _____ but still has some _____ activity, but NOT against ______.
gram positives; gram negative; Pseudomonas
Where are the amino acids changed on DNA gyrase and topo IV to create fluoroquinolone resistance?
quinolone-resistance-determining-region (QRDR)
What do quinolones target in gram - bacteria? gram + ones?
DNA gyrase; topo IV
How are aminoglycosides modified?
N-acetylation, O-nucleotidylation, O-phosphorylation
How do you treat bugs that carry ampC?
remember which ones they are ((Enterobacter, Pseudomonas- gram (-) rods)) and give a carbapenem
What does KPC stand for?
Klebsiella pneumoniae carbapenemase
How are the vanc resistant strains of S. aureus different?
- thickened peptidoglycan 2. less cross-linking
Which abx binds to the 23s portion of the 50s ribosome to inhibit peptide chain elongation?
the macrolides
What are the side effects to aminoglycosides?
ototox and renal tox
