DrugResistance

Question 1

Intrinsic resistance

Answer 1

Due to natural properties of bacteria / mech of drug

Question 2

Acquired resistance

Answer 2

Develops by genetic mutation or mobile genetic elements

Question 3

Mobile genetic elements

Answer 3

Plasmids, transposons, bacteriophages

Question 4

Broad categories of antibiotic resistance

Answer 4

(1) Inactivate/modify drug; (2) alter target; (3) reduce drug-target interaction

Question 5

Antibiotic susceptibilities

Answer 5

R (resistant) ? don’t use the drug; S (susceptible) ? the drug might work

Question 6

Porins

Answer 6

Hydrophilic channels in gram-neg outer membrane; mutation may impact drug uptake

Question 7

Efflux pumps

Answer 7

Pumps in cell membrane of both gram-pos and -neg; may pump out multiple classes of drugs

Question 8

Peptidoglycan

Answer 8

GlcNAc-MurNAc with 5 a.a. attached on MurNAc; assemble in cytoplasm, transported to membrane, surface

Question 9

Transpeptidation

Answer 9

Amino acid cross-linking (in peptidoglycans), usually cleaves last D-ala (from D-ala-D-ala)

Question 10

Transglycosylation

Answer 10

Joining of sugar molecules (in peptidoglycans)

Question 11

Bacterial gram-staining class assoc with resistance

Answer 11

Gram-neg

Question 12

Beta-lactam mech

Answer 12

Irreversibly binds PBPs and blocks transpeptidase fxn ? prevent peptide x-linking ? weaken cell wall ? ib cell growth

Question 13

Beta-lactam resistance

Answer 13

(1) beta-lactamase; (2) altered PBPs w/ low affinity; (3) porin AND drug efflux

Question 14

Beta-lactamases

Answer 14

Chr and plasmid; gram-pos and neg (most significantly gram-neg)

Question 15

?Narrow? beta-lactamases

Answer 15

S. aureus ?bla? plasmid; E. Coli TEM-1 plasmid; K. pneum. SHV-1 Chr (all vs PCN, amp)

Question 16

?Extended-spectrum beta-lactamases? (ESBLs)

Answer 16

mutants of TEM-1/2, SHV-1 allow more beta-lactams to ?fit?; mostly plasmid; primarily in E. coli and K. pneum

Question 17

ampC

Answer 17

Chr gene encodes beta-lactamase degradinging all penicillins, 1st-3rd gen cephalosporins; Enterobacter, Pseudomonas, Serratia

Question 18

ampC expression

Answer 18

Inducible by PCNs, 1st gen cephalosporins; Constitutive mutation ? breaks down all beta-lactams except carbapenems

Question 19

Carbapenemases

Answer 19

KPC and NDM-1; mostly in K. pneum. and E. coli

Question 20

Altered PBPs

Answer 20

(i) S. aureus ?mecA? PBP2a (=MRSA); (ii) Strep. Pneum. Mosaic PBP; (iii) Enterococci faecium PBP5

Question 21

Vancomycin mech

Answer 21

Binds terminal D-ala-D-ala, physically blocks PBPs ? disrupt cell wall synth ? cell death

Question 22

Vancomycin resistance ? enterococci

Answer 22

(2) VRE ?van? genes modify terminal D-ala-D-ala (e.g., vanA to D-ala-D-lac)

Question 23

Vancomycin resistance ? S. aureus

Answer 23

(3) VISA thick peptidoglycan cell walls w/ less x-linking ? free D-ala-D-ala soaks up vancomycin

Question 24

Quinolone mech

Answer 24

trap DNA gyrase or topoisomerase IV, resulting in release of lethal dsDNA breaks

Question 25

Quinolone mech ? gram-neg

Answer 25

DNA gyrase

Question 26

Quinolone mech ? gram-pos

Answer 26

Topoisomerase IV

Question 27

Quinolone drug spectrum

Answer 27

Cipro targets DNA gyrase, so gram-neg; Moxifloxacin targets topo IV, so gram-pos; Levofloxacin targets both

Question 28

QRDR

Answer 28

Quinolone resistance determining region

Question 29

Quinolone resistance

Answer 29

Step-wise process; (1) rare; (2) point mutations in QRDR of DNA gyrase / topo IV; (3) mostly drug efflux (vs fluoroquinolones)

Question 30

Macrolide mech

Answer 30

Bind to 23S rRNA component of 50S, preventing peptide chain elongation

Question 31

Macrolide resistance

Answer 31

(1) rare; (2) ?erm? gene dimethylase enzyme dimethylates 23S rRNA; (3) mostly Chr/plasmid drug efflux

Question 32

erm expression

Answer 32

Inducible by macrolides; constitutive affects macrolides but also clindamycin (same 23S rRNA binding site)

Question 33

D-test

Answer 33

if macrolide resistance is erm (and not efflux), get D shape (and therefore should avoid clindamycin as well)