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Microbiology Part 1 > Lec2 Antibiotic Strategies > Flashcards

Lec2 Antibiotic Strategies Flashcards

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1
Q

What are the four main classes of antibiotics?

A

inhibitors of

  • peptidoglycan [cell wall] synthesis
  • protein synthesis
  • polymerase activity
  • folic acid metabolism
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2
Q

What are 4 main beta-lactam antibiotics that affect peptidoglycan synthesis?

A
  • penicillin
  • cephalosporin
  • carbapenems
  • monobactam
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3
Q

Where does penicillin come from?

A
  • penicillium mold
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4
Q

Are gram + or - more affected by penicillin?

A

gram + because there is only one lipid bilayer to get through

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5
Q

How does penicillin work?

A

prevents synthesis of peptidoglycan cell wall by inhibiting transpeptidase that participates in cross-linking between parallel strands of murein

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6
Q

What is transpeptidase? Why is it significant?

A

an enzyme in bacterial cell wall that makes peptide cross-linking bonds to synthesize peptidoglycan
- it is inhibited by penicillin

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7
Q

What is significant in penicillin structure?

A
  • contains beta-lactam ring = internal peptide bond
  • contains two alanines within structure
  • mimics substrate structure so feeds into transpeptidase active site and blocks it
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8
Q

What are 3 important beta lactams?

A
  • penicillin
  • cephalosporin
    Cephamycin
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9
Q

What is beta-lactamase?

A
  • enzyme that makes bacteria resistant to beta lactams [aka penicillin, cephamycin, cephalosporin]
  • hydrolyzes the antibiotic beta-lactam structure
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10
Q

How do bacteria develop resistance?

A

via transposition of drug resistance genes and insertion of new sequences that code for nucleases so can cut the sequence to get circular segments of just the enzyme [penicilinase]
- the new r-determinant circular sequence that contains the enzyme can then be inserted into new plasmids to confer further drug resistance

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11
Q

What are two drugs that affect peptidoglycan synthesis?

A

vancomycin

bacitracin

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12
Q

What is mech of vancomycin?

A

recognizes ala and inhibits polymerization of peptidoglycan

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13
Q

What are two strategies of bacterial resistance to vancomycin?

A

strategy 1: decrease penetration of antibiotic to its target

strategy 2: alter target of antibiotic

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14
Q

What is significance of bacteria decreasing penetration of vancomycin?

A
  • gram negative bacteria intrinsically resistant because vancomycin cannot get across outer membrane
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15
Q

What is mech of vancomysin resistance? which bacteria commonly have this?

A
  • enterococci have plasma mediated resistance
  • enzymes synthesize D-ala-D-lactic instead of D-ala-D-ala so vancomycin cannot recognize its target and will not prevent polymerization
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16
Q

What are 3 types of antibiotics that affect membrane of cell wall?

A
  • polymyxins [cationic (+) detergents]
  • polyene antibiotics [amphotericine B bind to sterols]
  • azoles [inhibit cholesterol synthesis]
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17
Q

What is name for fungizone?

A

amphotericine B

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18
Q

What are 7 antibiotics that affect protein synthesis?

A
  • aminoglycosides
  • tetracyclins
  • cholramphenicol
  • macrolides [erythromycin]
  • linezolid
  • streptogramins
  • clindamycin
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19
Q

What is mech of aminoglycoside action? What are the 3 mechs of resistance?

A
  • affect protein synthesis
    1. decreased penetration of antibiotic to target
    2. alters target of antibiotic
    3. inactivates antibiotic [MAIN MECH] by changing structure
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20
Q

What is mech of tetracyclin action? What is mech of resistance?

A
  • affect protein synthesis

- transport of antibiotic out of cell

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21
Q

What is mech of chloramphenicol action? What is mech of resistance?

A
  • affect protein synthesis

- by acetyl-transferase CAT

22
Q

What is mech of macrolides [erythromycin] action? What is mech of resistance?

A
  • affect protein synthesis

- alters 50s ribosomal proteins, methylation of 23s RNA

23
Q

What is mech of linezolid action? What is mech of resistance?

A
  • affect protein synthesis

- changes 23s RNA

24
Q

What is mech of stretogramin action? What is mech of resistance?

A
  • affect protein synthesis

- efflux, modifies/inactivates target

25
Q

What is mech of clindamycin action? What is mech of resistance?

A
  • affect protein synthesis

- methylation of 23s RNA

26
Q

Which types of bacteria are intrinsically resistant to aminoglycosides? Why?

A

anaerobes and streptococci intrinsically resistant because active transport of aminoglycosides depends on e- transport chain

27
Q

Which type of aminoglycosides can be resisted by altering target of antibiotic?

A
  • streptomycin resistnace from 1 step mutation of 30s subunit
  • newr aminoglycosides very rare to get resistance this way because require several mutations to get resistance
28
Q

What is the most common resistance mech of aminoglycosides?

A
  • inactivation of the antibiotic
  • can be chromosome or plasmid mediated
  • most common = plasmid mediated
  • enzyme in bacteria DNA chemically modifies the antibiotic
29
Q

Which type of aminoglycoside is hardest to inactivate?

A
  • amikacin because it only has two sites that can be modified to inactivate
  • thus bacteria that resistant to other aminoglycosides may still be affected by amikacin
30
Q

What are 4 DNA-dependent DNA polymerase inhibitors?

A
  • quinolones
  • nalidixic acid
  • mitomycin
  • metronidazole
31
Q

What is mech of quinolones?

A
  • inhibits gyrase [cleave and allow twisting] and topoisomerase [unwinds DNA to make available to DNA polymerase]
  • specifically inhibit bacterial enzymes not the human versions
32
Q

What is mech of nalidixic acid?

A
  • inhibits gyrase
33
Q

What is mech of mitomycin?

A
  • cross-links DNA [not very specific for bacteria vs our own DNA]
34
Q

What is mech of metronidazole?

A
  • damages DNA by free radicals causes DNA fragmentation
  • not very specific for bacteria so can be very toxic
  • activated mostly under anaerobic conditions
  • imp for GI bacteria
35
Q

What are 2 drugs that inhibit DNA-dependent RNA polymerase?

A
  • rifampicin

- actinomycin D

36
Q

What is mech of rifampicin action?

A
  • binds to polymerase directly

- prevents initation complex of polymerase

37
Q

What is mech of actinomycin D actin?

A
  • intercalates DNA [slips between two strands of DNA so RNA polymerase can’t work]
38
Q

What are two folic acid antimetabolites?

A
  • sulfonamides

- trimethoprim

39
Q

What is mech of sulfonamides?

A
  • folic acid antimetabolite

- inhibits folic acid synthesis

40
Q

What is mech of trimethoprim?

A
  • folic acid antimetabolite
  • inhibits reduction of folic acid to THF [tetrahydrofolic acid]
  • produce more of enzy
41
Q

What do folic acids do?

A
  • needed for building of amino acids/proteins/DNA

- bacteria needs it to make its building blocks

42
Q

What are two mech of trimethoprim resistance?

A

enzyme overproduction or resistant enzyme

43
Q

What is mech of methicilin resistance?

A

loss of binding protein

44
Q

What is synergy vs indifference vs antagonism?

A

synergy- A+B get lower level of bacteria than A or B alone

indifference- A+B is basically the same as A cause B doesn’t do much

antagonism- A alone works, A in presence of B has less of an effect

45
Q

What is required for aminoglycosides to work? what does this mean for giving aminoglycoside + another protein synthesis inhibitor at same time?

A
  • in order for aminoglycoside to work you need to have protein synthesis occuring because thats what it inhibits
  • if you stop protein synthesis completely by giving another protein synthesis inhibitor at same time you get antagonism so not as good effect
46
Q

What does isoniazid treat?

A

treats TB

47
Q

What does pyrazinamide treat?

A

treats TB

48
Q

What does ethambutol treat?

A

treats TB

49
Q

What does pentamidine treat?

A

treats PCP pneumonia

50
Q

What does zyvox do?

A
  • protein synthesis inhibitor

- treats MRSA and vancomycin resistant strains

51
Q

what does synercid do?

A
  • protein synthesis inhibitor

- treats vancomycin resistant enterococcus

52
Q

What does tygacil do?

A
  • protein synthesis inhibitor

- treats MRSA

Microbiology Part 1 (24 decks)

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