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BI543—Pathogenic Microbiology > Exam 5—Antibiotics > Flashcards

Exam 5—Antibiotics Flashcards

1
Q

starting material for cell wall is ——-, which is turned into ——-

A

UDP-N-acetylglucosamine
N-acetyl muramic acid

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2
Q

——- side chain is added to cell wall after muramic acid

A

pentapeptide

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3
Q

in GPs, a ——- is added to L-lysine on cell wall

A

pentaglycine

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4
Q

binds and transports wall “units” across cytoplasmic membrane

A

bactoprenol (undeceprenyl)

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5
Q

transglycosylation creates…

A

creates the β1-4 bonds

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6
Q

transpeptidation creates…

A

creates peptide cross links between diaminopimelic acid and D-Ala (GNs) or D-Ala and Gly (GPs)

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7
Q

transpeptidation is performed by…

A

transpeptidase AKA penicilin-binding protein (PBP)

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8
Q

B-lactam target

A

PBP

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9
Q

—– makes an alternative PBP, to which B-lactams do not bind

A

MRSA

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10
Q

B-lactams inhibit the PBP, but what actually destroys the cell?

A

autolysins, destroying cell wall that the cell cannot replace

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11
Q

stimulate autolysin activity

A

free peptides

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12
Q

B-lactam drugs

A

penicillins
cephalosporins
carbapenems
monobactams

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13
Q

essential structure of B-lactam

A

warhead

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14
Q

glycopeptide/lipopeptide mechanism

A

Cell wall synth

Bind to D-Ala-D-Ala and inhibit both transglycosylation and transpeptidation

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15
Q

glycopeptide/lipopeptide drug

A

vancomycin

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16
Q

Vancomycin treats Gram —-

A

positives
especially MRSA

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17
Q

Fosfomycin & bacitracin mechanism

A

cell wall synth

Fosfomycin irreversibly inactivates enzyme that converts UDP-glucosamine to UDP-muramic acid

Bacitracin blocks recycling of bactroprenol

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18
Q

cell wall antibiotic only used topically

A

bacitracin

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19
Q

structure of fosfomycin

A

epoxide bridge

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20
Q

fosfomycin used to treat…

A

MRSA
UTIs

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21
Q

target 50s of ribosome

A

macrolides
chloramphenicol
lincosamides
streptogramins
everninomycins
oxazolidinones

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22
Q

target 30s of ribosome

A

aminoglycosides
tetracyclines

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23
Q

important in recognizing AUG start codon

A

30s

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24
Q

aminoglycoside mechanism

A

bind 16s rRNA of small subunit
large subunit is prevented from joining

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25
Q

aminoglycoside drugs

A

kanamycin
gentamicin

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26
Q

serious side effects of aminoglycosides

A

hearing loss
kidney impairment

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27
Q

tetracycline mechanism

A

Binds 16s rRNA of small subunit
large subunit joins, but A site is distorted, and tRNA cannot align with codon on mRNA

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28
Q

tetracycline used to treat…

A

Lyme
chlamydia
gonorrhea
acne
in animal feed

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29
Q

side effect of tetracycline

A

graying of teeth if used for longer periods

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30
Q

macrolide drugs

A

erythromicin
azithromycin

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31
Q

macrolide mechanism

A

23s rRNA of large subunit, blocking the exit tunnel

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32
Q

erythromycin use

A

animal feed

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33
Q

azithromycin use

A

chlamydia
gonorrhea

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34
Q

advantage of azithromycin, used for sex workers

A

long lasting with only one or two doses needed

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35
Q

lincosamide mechanism

A

binds 23S rRNA of large subunit, blocking the exit tunnel

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36
Q

lincosamide drug

A

clindamycin

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37
Q

clindamycin use

A

obligate anaerobes
Bacteroides
Giardia parasite
C. difficile

38
Q

nucleic acid synth inhibitors are ——- inhibitors

A

DNA gyrase (topoisomerase I and II)

39
Q

DNA gyrase drugs

A

quinalone
norfloxacin
ciprofloxacin
fluoroquinalone

40
Q

part of quinalone that inhibits DNA gyrase

A

nalidixic acid

41
Q

gyrase inhibitor mechanism

A

this induces cleavage of DNA and inhibits closing of nicks formed in supercoiling mechanism
DNA cannot be packaged into new cell

42
Q

best tx for anthrax

A

fluoroquinalone/cipro

43
Q

fluoroquinalone/cipro makes a good choice because of poor action against…

A

microbiota

44
Q

metronidazole mechanism

A

active form degrades DNA

45
Q

inactive form of metronidazole is taken, and it is converted to active form by…

A

ferredoxins and flavodoxins found in obligate anaerobes (not in human cells)

46
Q

metronidazole used against…

A

amitochondriate parasites Giardia and Trichomonas

47
Q

RNA synthesis drug

A

rifampin

48
Q

rifampin mechanism

A

binds β-subunit of core polypeptide of RNA polymerase in bacteria

blocks mRNA exit tunnel

49
Q

rifampin used against….

A

M. tuberculosis

50
Q

folic acid synth drugs

A

sulfonamides
trimethoprim

51
Q

folic acid required for…

A

1-C metabolism in nucleic acid and protein synthesis

52
Q

Prototrophic bacteria synthesize folic acid from —-

A

PABA

53
Q

sulfonamide mechanism

A

analogs of PABA and inhibit dihydropteroid acid synthesis

54
Q

trimethoprim mechanism

A

analog of dihydrofolate and inhibits dihydrofolate reductase

55
Q

SXT =

A

sulfonamide + trimethoprim

56
Q

SXT used to ID…

A

Used to identify S. pneumoniae (susceptible) and S. pyogenes/S. agalactiae (resistant)

57
Q

4 main methods of resistance

A
  • modification of target
  • limiting access
  • enzymatic inactivation
  • failure to activate drug
58
Q

limiting access strategies

A

outer membrane porin reduction
reduced uptake
active efflux

59
Q

allow drug entry to periplasm of GNs

A

porins

60
Q

how can mutation change porins for resistance?

A

Mutation can eliminate porins, reduce diameter, prevent uptake, or decrease expression

61
Q

mutations not involved in preventing uptake of ——-

A

aminoglycosides

62
Q

——– are not affected by limiting access method of resistsance

A

B lactams (and other cell wall synth inhibitors)

tetracyclines (hydrophobic, cross membrane without transporter)

63
Q

mechanism under which bacteria can change expression of transport proteins for drugs

example

A

differential expression

E. coli makes transporter for aminoglycosides 10x less under anaerobic conditions, and not suscepible

64
Q

E. coli and P. aeruginosa express around 30 efflux pumps to remove a variety of substances, including…..

A

tetracyclines
macrolides

65
Q

TetA

A

tetraclycline efflux pump

66
Q

H+ driven antiporter for active efflux

A

Resistance-nodulation cell division (RND)

67
Q

ATP-driven efflux pump related to T1SS

A

ABC system

68
Q

lactamase

A

degrade lactam rings

69
Q

augmenters that inhibit lactamase and increase effectiveness of drug

A

clavulanic acid
sulbactam

70
Q

lactamases that resist augmenters

A

zinc lactamases

71
Q

part of lactamase vulnerable to augmenters

A

serine

72
Q

kanamycin mods which reduce its action

A

acetylation, phosphorylation, and adenylation

73
Q

Chloramphenicol acetyltransferase (CAT)

A

Addition of acetyl group prevents binding of chloramphenicol to 23s rRNA pepidyltransferase, and therefore exit site of ribosome is not blocked

74
Q

TetX gene

A

codes for an NADPH-dependent oxidoreductase that forms an epoxide and inactivates the tetracycline

75
Q

Tetracycline reductases

A

cleave a ring of drug

76
Q

positive side of tetracycline enzymatic inactivators

A

only found in soil bacteria, not in clinical pathogens yet

77
Q

TetM, TetO, TetQ

A

protect ribosome from tetracycline

homology with elongation factors and GTPase activity - they change shape of 16s rRNA, which decreases tetracycline binding

78
Q

mecA

A

makes PBP2’ in MRSA, which does not bind to warhead

79
Q

other species with no lactamase activity, but instead an altered PBP

A

S. pneumoniae

80
Q

how does Enterococcus resist vanc?

A

modification of peptidoglycan cross-links

81
Q

VRE resistance mechanism

A

Peptide usually ends in D-Ala-D-Ala, which vancomycin binds to, but VRE (vancomycin resistant Enterococcus) makes a D-Ala-D-lactate variant

does not bind vancomycin, so transpeptidation can proceed

82
Q

function of enzymes in VRE resistance to vanc

A

VanH makes the lactate from pyruvate
VanA attaches D-Ala to D-lactate
VanX and VanY cleave D-Ala-D-Ala in free peptide or in the crosslinks

83
Q

RNA methylases (ErmA, ErmB, etc)

A

confer resistance to erythromycin by methylating adenine 2058 on 23rRNA

84
Q

mutation way of resisting erythromycin

A

adenine 2058 can mutate to guanine

85
Q

allows resistance to gyrase inhibitors

A

mutation in A or B subunits

86
Q

allows resistance to rifampin

A

mutation in the B-subunit of RNA polymerase

87
Q

allows resistance to streptomycin

A

mutation in the rpsL gene for protein S12 results in a protein that does not bind streptomycin

88
Q

allows resistance to metronidazole

A

reduced expression of flavodoxins

89
Q

isoniazid mechanism
(mycobacteria)

A

drug activated by catalase KatG, and the product forms an adduct with carrier InhA

adduct inhibits mycolic acid synthesis

90
Q

allows resistance to isoniazid

A

KatG is inactivated, or when the gene is deleted or expression is reduced

91
Q

allows resistance to sulfa drugs

A

mutation in DHPS (dihydropteroate synthase) gene

92
Q

allows resistance to trimethoprim

A

mutation in DHFR (dihydrofolate reductase) gene

BI543—Pathogenic Microbiology (10 decks)

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