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Which antibiotics inhibit cell wall synthesis? (7)
- 1- Beta-lactam
- 2- Televancin
- 3- Dalbavancin
- 4- Cycloserine
- 5- Vancomycin
- 6- Bacitracin
- 7- Fosfomycin
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Which type of cell wall has teichoic acid?
Gram +
-
Simple cell wall
High internal osmolarity
Thick peptidoglycan layer
Gram + cell wall
-
Complex cell wall
Low internal osmolarity
Thin peptidoglycan layer
Gram - cell wall
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A 5 amino acid peptide is linked to the ______ acid sugar
NAM
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AKA murein or mucopeptide
peptidoglycan polymer
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This ______ acid sugar terminates at the D-Al, D-Al
NAM
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What gives the bacterial cell wall structural ridigity?
Cross-linked peptide side chains
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Linear polymeric chains must be cross-linked by ___________ for cell viability
transpeptidation
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AKA Lipid II
NAG-NAM-pentapeptide
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What tethers the Lipid II?
Bactroprenol (lipid-linker)
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Lipid II is transferred from the ____ of the cell to the ______
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Lipid II is grafted onto the cell-wall via enzymes called _________________
PBPs (Penicillin Binding Proteins)
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PBP is a bifunctional enzyme with 2 separate domains, what are the 2 domains?
- 1- transpeptidase domain
- 2- glycosyltransferase domain
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What is the function of the transpeptidase domain?
Catalyzes the cross-linking step (transpeptidation)
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Only the ___________ domain is inhibted by beta-lactam antibiotics.
transpeptidase
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The transpeptidase (c-terminal) domain is on the _______ of the cell so that it can find its substrate ___________
- outside
- pentapeptide side chains
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What is the function of the glycosyltransferase (N-terminal) domain of the PBP?
It catalyzes the transglycosylation step
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What is transglycosylation step?
NAM in the Lipid II is attached to the NAG via a glycosidic linkage
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AKA C-O-C linkage
glycosidic linkage
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True or false, transpeptidase is membrane bound.
False, glycosyltransferase is membrane bound, transpeptidase is connected to the glycosyltansferase via a linker (bactoprenol)
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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
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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)
-
Responsible for the formation of the D-Al--D-Al dipeptide
D-alanyl-D-alanine ligase
-
Converts L-Al to D-Al
alanine racemase
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Inhibits the dephosphorylation step in the cycling of bactoprenol which inhibits the attachment of NAM to the membrane
Bacitracin
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Binds to the D-Al--D-Al terminus
Inhibits both transglycosylation and transpeptidation
(2 drugs)
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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
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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
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Which 2 drugs have a long lipophilic side chain?
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Inhibits the cross-linking step by covalently binding to the transpeptidase domain of PBPs inhbiting the transpeptidation reaction
Beta-lactams
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VRSA and enterococci have developed resistance to vancomycin by...?
Target modification via replacing the D-Al with D-lactate
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PBPs catalyze transpeptidation how?
By cleaving the terminal D-Al allowing for cross-linking
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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
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Structural analogs of natural (D-Al--D-Al) substrate for PBPs
Beta-lactams
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What is classical cross-resistance?
A single resistance mechanism that confers resistance to only 1 class of antibiotics
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Methylation of a single adenine in rRNA confers resistance to macrolides, lincosamides, and streptogramins---this is an example of?
overlapping targets
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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
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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
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Which antibiotics inhibit nucleic acid synthesis? (2)
- 1- Quinolones
- 2- Rifamycins
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Which antibiotics disrupt cell membrane permiability? (2)
- 1- polypeptides
- 2- cyclic lipopeptides
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Which antibiotics are antifolates? (2)
- 1- sulfonamides
- 2- trimethoprim
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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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