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Lindsey's D&D Unit 3 > Mechanisms of Antimicrobial Resistance > Flashcards

Mechanisms of Antimicrobial Resistance Flashcards

1
Q

The enzymes that perform cross-linking of peptidoglycan are called _____.

A

penicillin binding proteins (PBPs)

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2
Q

How does S. aureus prevent target-drug interaction in vancomycin resistance?

A

free vancomycin is bound in the existing peptidoglycan cell wall

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3
Q

What are efflux pumps?

A

structures in bacterial cell membranes that eliminate certain substances, incl. abx

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4
Q

How do bacteria prevent target-drug interaction in vancomycin resistance?

A

free vancomycin is bound in the existing peptidoglycan cell wall

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5
Q

The peptidoglycan precursor ends in _____.

A

2 D-alanines

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5
Q

_____ are β-lactam antibiotics with the broadest spectrum of activity against most gram - rods.

A

Carbapenems

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5
Q

Name 2 broad ways bacteria can become resistant to vancomycin.

A
  1. modifying the target 2. preventing target-drug interaction
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6
Q

_____ are structures in bacterial cell membranes that eliminate certain substances, incl. abx.

A

Efflux pumps

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7
Q

What does PBP stand for?

A

penicillin-binding proteins

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7
Q

Which drug induces erm?

A

macrolides

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8
Q

ESBLs are mostly found in ____, exclusively in _____.

A

plasmids; gram - rods

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9
Q

What are β-lactamases?

A

enzymes that inactivate β-lactam Abx by splitting the amide bond

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9
Q

What is the tx for species that express ampC?

A

carbapenems

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9
Q

How does Enterococcus spp become vanc resistant?

A

it changes the 5 member peptide that hangs off MurNAc so vancomycin cant recognize it

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10
Q

If erm is constitutively expressed, the bacteria will be resistant to _____. If erm is inducably expressed, the bacteria will be resistant to _____.

A

macrolides and clindamycin; macrolides only

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11
Q

Carbapenemases causing the most problems are plasmid-mediated and are found mainly in some _____ isolates, although transfer to ____ has occurred.

A

Klebsiella pneumoniae; E. coli

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12
Q

Give an example of intrinsic resistance.

A

vancomycin resistance of gram- organisms b/c it can’t penetrate the outer membrane

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13
Q

Where are porins found?

A

in the outer membrane of gram - bacteria

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15
Q

What is intrinsic resistance?

A

occurs just because via natural properties of the bacteria

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16
Q

β-lactamases are found in both gram + and gram - bacteria, but the worse ones are in the _____.

A

gram -

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16
Q

What is KPC?

A

Klebsiella pneumoniae carbapenemase- hydrolyzes all carbapenems and all other β-lactams

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16
Q

____ targets DNA gyrase as well as Cipro but also targets topo IV.

A

Levofloxacin

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17
Q

Carbapenemases causing the most problems are ____ and are found mainly in some Klebsiella pneumoniae isolates, although transfer to E. coli has occurred.

A

plasmid-mediated

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18
Q

What is mecA?

A

gene staph has that encodes a different PBP- causes MRSA

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19
Q

What does ESBL stand for?

A

extended spectrum beta-lactamases

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20
Q

Efflux pumps are found in _____ and _____ bacteria.

A

gram -, gram +

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20
Q

Anaerobic bacteria are inherently resistant to _____.

A

aminoglycosides

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21
Q

What do porins do?

A

form hydrophilic channels to allow selective uptake of nutrients, including some Abx

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21
Q

What is the D test?

A

distinguishes between erm and efflux-based resistance in bacteria; erm = D shape colony growth

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22
Q

____ is much for effective for gram negative bacteria than gram positives.

A

Cipro

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23
Q

During peptidoglycan cross linking, a ____ is cleaved

A

D-alanine

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23
Q

PBPs perform _____ and/or _____ reactions.

A

transpeptidase; transglycosylase

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24
Q

How are mecA staph treated?

A

5th gen cephalosporin

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25
Q

Carbapenems are β-lactam antibiotics with the broadest spectrum of activity against most ____.

A

gram - rods

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25
Q

_____ causing the most problems are plasmid-mediated and are found mainly in some Klebsiella pneumoniae isolates, although transfer to E. coli has occurred.

A

Carbapenemases

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26
Q

What does ampC encode? Why is it unique?

A

a β-lactamse that can hydrolyze penicillins, cephalosporins, and is not inhibited by beta-lactamase inhibitors

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28
Q

Where is ampC found?

A

the chromosome of gram - rods (Enterobacter, Pseudomonas)

29
Q

Cipro is much more effective against _____ bacteria than _____ ones.

A

gram negative; gram positive

30
Q

Name 2 ways bacteria become resistant to macrolides.

A
  1. methylate the 23s ribosome via erm gene 2. prevent drug-drug interaction via efflux pumps
32
Q

______ act by irreversibly binding and inactivating the transpeptidase reaction of PBPs, thereby inhibiting peptide cross-linking and peptidoglycan synthesis.

A

β-lactam antibiotics

33
Q

Where are the β-lactamase genes located?

A

on chromosomes (Klebsiella pneumoniae) or on plasmids (Staph. aureus, E. coli, H. influenzae)

34
Q

Where is the erm gene found?

A

on transposons or plasmids

36
Q

Name 3 ways bacteria become resistant to β-lactam antibiotics.

A
  1. modify the drug (enzymatic destruction) 2. modify the target (alter the PBPs) 3. prevent drug-target interaction (porins and efflux mechanisms)
37
Q

_____ occurs just because, via natural properties of the bacteria.

A

Intrinsic resistance

38
Q

ampC expression is either ____ or _____.

A

inducible, constitutive

39
Q

β-lactam antibiotics act by irreversibly binding and inactivating the transpeptidase reaction of PBPs, thereby inhibiting ____ and _____.

A

peptide cross-linking; peptidoglycan synthesis

41
Q

____ is due to genetic mutations or acquisition of new genes (plasmids, bacteriophages, transposons).

A

Acquired resistance

42
Q

What are the 3 major mechanisms of resistance?

A
  1. inactivation/modification of the drug 2. altered antibacterial target 3. reduced drug delivery to the target
43
Q

______ is formed by the addition of subunits called precursors (GlcNAc-MurNAc with 5 aas on the MurNAc).

A

Peptidoglycan

44
Q

____ targets topo IV preferentially; it’s best against gram positives but still has some gram negative activity, but NOT against Pseudomonas.

A

Moxifloxacin

45
Q

How do bacteria modify the target in vancomycin resistance?

A

change the 5 member peptide that hangs off MurNAc so vancomycin cant recognize it

45
Q

_____ has good gram negative activity and much improved gram positive activity.

A

Levofloxacin

47
Q

Peptidoglycan is formed by the addition of subunits called precursors (_____ with 5 aas on the _____).

A

GlcNAc-MurNAc; MurNAc

48
Q

How do macrolides work?

A

bind to the 23s portion of the 50s ribosome to inhibit peptide chain elongation

49
Q

What do narrow spectrum β-lactamases do?

A

hydrolize penicillin-type Abx

49
Q

What do the vanA and vanB genes in VRE do?

A

change the peptide chain from D-ala, D-ala to D-ala, D-lactate

51
Q

β-lactam antibiotics act by irreversibly binding and inactivating the _____ reaction of PBPs, thereby inhibiting peptide cross-linking and peptidoglycan synthesis.

A

transpeptidase

52
Q

Cipro preferentially targets ____ over ____.

A

DNA gyrase; topo IV

53
Q

What genes do VRE have that encode their vanc resistance? Where are they located?

A

vanA and van B; plasmids

54
Q

____ perform transpeptidase and/or transglycosylase reactions.

A

PBPs

55
Q

Which bacteria changes the 5 member peptide that hangs off MurNAc so vancomycin cant recognize it?

A

enterococcus (VRE)

57
Q

Which bugs have mosaic PBPs?

A

Strep. pneumonia and N. gonorrhoeae

59
Q

Where is NDM-1 found?

A

on plasmids

60
Q

What is acquired resistance?

A

genetic mutation or acquisition of new genes (plasmids, bacteriophages, transposons)

61
Q

Changes in porins or efflux pumps may cause ____.

A

changed uptake of Abx

62
Q

Where is KPC found?

A

on plasmids

62
Q

Levofloxacin targets DNA gyrase as well as Cipro but also targets ____.

A

topo IV

63
Q

How can bacteria become resistant to fluoroquinolones?

A

change amino acids in DNA gyrase and topo; drug efflux

64
Q

Moxifloxacin targets _____ preferentially; it’s best against gram positives but still has some gram negative activity, but NOT against Pseudomonas.

A

topo IV

64
Q

_____ are inherently resistant to aminoglycosides.

A

Anaerobic bacteria

65
Q

DNA gyrase is targeted by quinolones in _____ bacteria; topo IV is targeted by them in _____.

A

gram (-); gram (+)

66
Q

Methylation of the ribosome confers resistance to ____ and ____ Abx.

A

macrolides; clindamycin

68
Q

Carbapenems are _____ with the broadest spectrum of activity against most gram - rods.

A

β-lactam antibiotics

71
Q

Extended spectrum beta-lactamases (ESBLs) are notable bc they can attack most ___.

A

cephalosporins

72
Q

What is NDM-1?

A

enzyme that hydrolyzes all β-lactams except aztreonam

73
Q

Levofloxacin has good ____ activity and much improved _____ activity.

A

gram negative; gram positive

74
Q

What does a carbapenem treat?

A

gram - rods

75
Q

_____ preferentially targets DNA gyrase over topo IV.

A

Cipro

76
Q

How are mosaic PBPs formed?

A

by picking up naked DNA from the environment and swapping them for similar pieces of their own PBP DNA

77
Q

Peptidoglycan is formed by the addition of subunits called _____ (GlcNAc-MurNAc with 5 aas on the MurNAc).

A

precursors

78
Q

What are penicillin binding proteins (PBPs)?

A

enzymes that cross-link peptidoglycan

80
Q

Which bacteria binds free vancomycin up in the cell wall, preventing its action?

A

S. aureus

81
Q

Moxifloxacin targets topo IV preferentially; it’s best against _____ but still has some _____ activity, but NOT against ______.

A

gram positives; gram negative; Pseudomonas

82
Q

Where are the amino acids changed on DNA gyrase and topo IV to create fluoroquinolone resistance?

A

quinolone-resistance-determining-region (QRDR)

84
Q

What do quinolones target in gram - bacteria? gram + ones?

A

DNA gyrase; topo IV

85
Q

How are aminoglycosides modified?

A

N-acetylation, O-nucleotidylation, O-phosphorylation

86
Q

How do you treat bugs that carry ampC?

A

remember which ones they are ((Enterobacter, Pseudomonas- gram (-) rods)) and give a carbapenem

87
Q

What does KPC stand for?

A

Klebsiella pneumoniae carbapenemase

89
Q

How are the vanc resistant strains of S. aureus different?

A
  1. thickened peptidoglycan 2. less cross-linking
90
Q

Which abx binds to the 23s portion of the 50s ribosome to inhibit peptide chain elongation?

A

the macrolides

91
Q

What are the side effects to aminoglycosides?

A

ototox and renal tox

Lindsey's D&D Unit 3 (12 decks)

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