ANTIBIOTICS-2 (plus the end of ANTIBIOTICS-1)

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ANTIBIOTICS-2 (plus the end of ANTIBIOTICS-1)
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2011-02-13 14:55:24
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  1. Which antibiotics inhibit cell wall synthesis? (7)
    • 1- Beta-lactam
    • 2- Televancin
    • 3- Dalbavancin
    • 4- Cycloserine
    • 5- Vancomycin
    • 6- Bacitracin
    • 7- Fosfomycin
  2. Which type of cell wall has teichoic acid?
    Gram +
  3. Simple cell wall
    High internal osmolarity
    Thick peptidoglycan layer
    Gram + cell wall
  4. Complex cell wall
    Low internal osmolarity
    Thin peptidoglycan layer
    Gram - cell wall
  5. A 5 amino acid peptide is linked to the ______ acid sugar
    NAM
  6. AKA murein or mucopeptide
    peptidoglycan polymer
  7. This ______ acid sugar terminates at the D-Al, D-Al
    NAM
  8. What gives the bacterial cell wall structural ridigity?
    Cross-linked peptide side chains
  9. Linear polymeric chains must be cross-linked by ___________ for cell viability
    transpeptidation
  10. AKA Lipid II
    NAG-NAM-pentapeptide
  11. What tethers the Lipid II?
    Bactroprenol (lipid-linker)
  12. Lipid II is transferred from the ____ of the cell to the ______
    • Inside
    • Outside
  13. Lipid II is grafted onto the cell-wall via enzymes called _________________
    PBPs (Penicillin Binding Proteins)
  14. PBP is a bifunctional enzyme with 2 separate domains, what are the 2 domains?
    • 1- transpeptidase domain
    • 2- glycosyltransferase domain
  15. What is the function of the transpeptidase domain?
    Catalyzes the cross-linking step (transpeptidation)
  16. Only the ___________ domain is inhibted by beta-lactam antibiotics.
    transpeptidase
  17. The transpeptidase (c-terminal) domain is on the _______ of the cell so that it can find its substrate ___________
    • outside
    • pentapeptide side chains
  18. What is the function of the glycosyltransferase (N-terminal) domain of the PBP?
    It catalyzes the transglycosylation step
  19. What is transglycosylation step?
    NAM in the Lipid II is attached to the NAG via a glycosidic linkage
  20. AKA C-O-C linkage
    glycosidic linkage
  21. True or false, transpeptidase is membrane bound.
    False, glycosyltransferase is membrane bound, transpeptidase is connected to the glycosyltansferase via a linker (bactoprenol)
  22. Inhibits the conversion of the NAG to NAM by inhibiting enolpyruvate transferase enzyme

    Binds covalently to the active site of the enzyme and blocks the addition of PEP to NAG
    Fosfomycin
  23. Inhibits the incorporation of D-Al to the peptidoglycan pentapeptide by inhibiting alanine racemase

    ALSO

    Inhibits D-alanyl-D-alanine ligase
    Cycloserine (structural analog of D-Al)
  24. Responsible for the formation of the D-Al--D-Al dipeptide
    D-alanyl-D-alanine ligase
  25. Converts L-Al to D-Al
    alanine racemase
  26. Inhibits the dephosphorylation step in the cycling of bactoprenol which inhibits the attachment of NAM to the membrane
    Bacitracin
  27. Binds to the D-Al--D-Al terminus

    Inhibits both transglycosylation and transpeptidation

    (2 drugs)
    • Vancomycin
    • Dalbavancin
  28. What is difference between vancomycin and dalbavancin? (2)
    • Dalbavancin has a higher affinity for binding to the D-Al--D-Al terminus
    • ALSO
    • Dalbavancin has a lipophilic side chain which acts as a membrane anchor
  29. Binds to D-Al--D-Al terminus inhibiting transglycosylation and transpeptidation

    AND

    Depolarizes the cell membrane with its lipophilic side chain disrupting functional integrity
    Telavancin
  30. Which 2 drugs have a long lipophilic side chain?
    • Telavancin
    • Dalbavancin
  31. Inhibits the cross-linking step by covalently binding to the transpeptidase domain of PBPs inhbiting the transpeptidation reaction
    Beta-lactams
  32. VRSA and enterococci have developed resistance to vancomycin by...?
    Target modification via replacing the D-Al with D-lactate
  33. PBPs catalyze transpeptidation how?
    By cleaving the terminal D-Al allowing for cross-linking
  34. True or false, antibiotics that inhibit cell wall synthesis are cidal when the cell is not dividing.
    False, the antibiotics are cidal only when the bacteria are dividing
  35. Structural analogs of natural (D-Al--D-Al) substrate for PBPs
    Beta-lactams
  36. What is classical cross-resistance?
    A single resistance mechanism that confers resistance to only 1 class of antibiotics
  37. Methylation of a single adenine in rRNA confers resistance to macrolides, lincosamides, and streptogramins---this is an example of?
    overlapping targets
  38. What is active efflux?
    • ATP dependent transport pumps that confers resistance to antibiotics by pumping them out of the cell
    • Can be specific/non-specific
  39. What is co-resistance?
    • The worst kind of resistance
    • The presence of several resistance mechanisims conferring resistance

    co-expression of various genes will allow for co-selection for resistance
  40. Which antibiotics inhibit nucleic acid synthesis? (2)
    • 1- Quinolones
    • 2- Rifamycins
  41. Which antibiotics disrupt cell membrane permiability? (2)
    • 1- polypeptides
    • 2- cyclic lipopeptides
  42. Which antibiotics are antifolates? (2)
    • 1- sulfonamides
    • 2- trimethoprim
  43. Which antibiotics are inhibitors of protein synthesis? (8)
    • 1- Tetracyclines
    • 2- Aminoglycosides
    • 3- Macrolides
    • 4- Lincosamides
    • 5- Chloramphenicol
    • 6- Streptogramins
    • 7- Linezolid
    • 8- Pleuromutilins

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