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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
aminoglycoside drugs
kanamycin gentamicin
26
serious side effects of aminoglycosides
hearing loss kidney impairment
27
tetracycline mechanism
Binds 16s rRNA of small subunit large subunit joins, but A site is distorted, and tRNA cannot align with codon on mRNA
28
tetracycline used to treat...
Lyme chlamydia gonorrhea acne in animal feed
29
side effect of tetracycline
graying of teeth if used for longer periods
30
macrolide drugs
erythromicin azithromycin
31
macrolide mechanism
23s rRNA of large subunit, blocking the exit tunnel
32
erythromycin use
animal feed
33
azithromycin use
chlamydia gonorrhea
34
advantage of azithromycin, used for sex workers
long lasting with only one or two doses needed
35
lincosamide mechanism
binds 23S rRNA of large subunit, blocking the exit tunnel
36
lincosamide drug
clindamycin
37
clindamycin use
obligate anaerobes Bacteroides Giardia parasite C. difficile
38
nucleic acid synth inhibitors are ------- inhibitors
DNA gyrase (topoisomerase I and II)
39
DNA gyrase drugs
quinalone norfloxacin ciprofloxacin fluoroquinalone
40
part of quinalone that inhibits DNA gyrase
nalidixic acid
41
gyrase inhibitor mechanism
this induces cleavage of DNA and inhibits closing of nicks formed in supercoiling mechanism DNA cannot be packaged into new cell
42
best tx for anthrax
fluoroquinalone/cipro
43
fluoroquinalone/cipro makes a good choice because of poor action against...
microbiota
44
metronidazole mechanism
active form degrades DNA
45
inactive form of metronidazole is taken, and it is converted to active form by...
ferredoxins and flavodoxins found in obligate anaerobes (not in human cells)
46
metronidazole used against...
amitochondriate parasites Giardia and Trichomonas
47
RNA synthesis drug
rifampin
48
rifampin mechanism
binds β-subunit of core polypeptide of RNA polymerase in bacteria blocks mRNA exit tunnel
49
rifampin used against....
M. tuberculosis
50
folic acid synth drugs
sulfonamides trimethoprim
51
folic acid required for...
1-C metabolism in nucleic acid and protein synthesis
52
Prototrophic bacteria synthesize folic acid from ----
PABA
53
sulfonamide mechanism
analogs of PABA and inhibit dihydropteroid acid synthesis
54
trimethoprim mechanism
analog of dihydrofolate and inhibits dihydrofolate reductase
55
SXT =
sulfonamide + trimethoprim
56
SXT used to ID...
Used to identify S. pneumoniae (susceptible) and S. pyogenes/S. agalactiae (resistant)
57
4 main methods of resistance
- modification of target - limiting access - enzymatic inactivation - failure to activate drug
58
limiting access strategies
outer membrane porin reduction reduced uptake active efflux
59
allow drug entry to periplasm of GNs
porins
60
how can mutation change porins for resistance?
Mutation can eliminate porins, reduce diameter, prevent uptake, or decrease expression
61
mutations not involved in preventing uptake of -------
aminoglycosides
62
-------- are not affected by limiting access method of resistsance
B lactams (and other cell wall synth inhibitors) tetracyclines (hydrophobic, cross membrane without transporter)
63
mechanism under which bacteria can change expression of transport proteins for drugs example
differential expression E. coli makes transporter for aminoglycosides 10x less under anaerobic conditions, and not suscepible
64
E. coli and P. aeruginosa express around 30 efflux pumps to remove a variety of substances, including.....
tetracyclines macrolides
65
TetA
tetraclycline efflux pump
66
H+ driven antiporter for active efflux
Resistance-nodulation cell division (RND)
67
ATP-driven efflux pump related to T1SS
ABC system
68
lactamase
degrade lactam rings
69
augmenters that inhibit lactamase and increase effectiveness of drug
clavulanic acid sulbactam
70
lactamases that resist augmenters
zinc lactamases
71
part of lactamase vulnerable to augmenters
serine
72
kanamycin mods which reduce its action
acetylation, phosphorylation, and adenylation
73
Chloramphenicol acetyltransferase (CAT)
Addition of acetyl group prevents binding of chloramphenicol to 23s rRNA pepidyltransferase, and therefore exit site of ribosome is not blocked
74
TetX gene
codes for an NADPH-dependent oxidoreductase that forms an epoxide and inactivates the tetracycline
75
Tetracycline reductases
cleave a ring of drug
76
positive side of tetracycline enzymatic inactivators
only found in soil bacteria, not in clinical pathogens yet
77
TetM, TetO, TetQ
protect ribosome from tetracycline homology with elongation factors and GTPase activity - they change shape of 16s rRNA, which decreases tetracycline binding
78
mecA
makes PBP2’ in MRSA, which does not bind to warhead
79
other species with no lactamase activity, but instead an altered PBP
S. pneumoniae
80
how does Enterococcus resist vanc?
modification of peptidoglycan cross-links
81
VRE resistance mechanism
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
function of enzymes in VRE resistance to vanc
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
RNA methylases (ErmA, ErmB, etc)
confer resistance to erythromycin by methylating adenine 2058 on 23rRNA
84
mutation way of resisting erythromycin
adenine 2058 can mutate to guanine
85
allows resistance to gyrase inhibitors
mutation in A or B subunits
86
allows resistance to rifampin
mutation in the B-subunit of RNA polymerase
87
allows resistance to streptomycin
mutation in the rpsL gene for protein S12 results in a protein that does not bind streptomycin
88
allows resistance to metronidazole
reduced expression of flavodoxins
89
isoniazid mechanism (mycobacteria)
drug activated by catalase KatG, and the product forms an adduct with carrier InhA adduct inhibits mycolic acid synthesis
90
allows resistance to isoniazid
KatG is inactivated, or when the gene is deleted or expression is reduced
91
allows resistance to sulfa drugs
mutation in DHPS (dihydropteroate synthase) gene
92
allows resistance to trimethoprim
mutation in DHFR (dihydrofolate reductase) gene

BI543—Pathogenic Microbiology (10 decks)

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