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