Antimicrobial Agents Flashcards
What enzyme do B-lactams inhibit, and what does it do?
- blocks transpeptidase
- normally cross-links Muramic acid via their D-ala-D-ala portions (peptidoglycans)
What, on bacteria, does penicillin look like?
D-ala-D-ala
TEM
B-lactamase
TEM TEM TEM
TEM TEM
TEM
What are the glycopeptide antimicrobials?
- Vancomycin
- teicoplanin
What type of bacteria are intrinsically resistant to Vancomycin?
Gram (-) bacteria
What does Vancomycin bind to?
D-ala-D-ala
-Blocks cross-linking reaction
What is the phenotype of vancomycin resistance?
D-ala-D-ala → D-ala-D-lac
What is Vancomycin Intermediate S. aureus (VISA)?
- Characterized by thickening of cell wall.
- Thicker cell wall has more D-ala-D-ala in outer layer of peptidoglycan which can trap vancomycin.
What is cycloserine?
- cell wall synthesis inhibitor
- blocks D-ala ligase
*needs to enter cytoplasm
Which antibiotics inhibits the 30s segment of bacterial ribosomes?
- Aminoglycosides
- Tetracyclines
- Tigecycline
How do aminoglycosides work?
-Bind to 30 S subunit of ribosome and prevent formation of initiation complex
How is bacterial resistance to aminoglycocides mediated?
- Enzymatic inactivation of the drug
- A set of plasmid encoded enzymes can adenylate, phosphorylate or acetylate aminoglycosides
How do tetracyclines work?
Attach to 30 S subunit to prevent binding of incoming aminoacyl-tRNA
How is bacterial resistance to tetracyclines work?
- active efflux of the drug out of the bacteria
- also by a plasmid-encoded tetracycline binding protein
How do macrolides work?
Bind 50S subunit and block translocation.
How do lincosamides work?
Bind 50S subunit and block translocation.
What classes of antibiotics bind the 50s subunit of bacterial ribososmes?
- Macrolides
- Lincosamides
- spectinomycin
- Chloramphenicol
- oxazolidinomes
What is the bacterial mechanism for resistance to macrolides and lincosamides?
-altered target site
How does chloramphenicol work?
- binds 50s subunit of ribosome
- inhibits peptidyl transferase to block peptide bond formation
What is the bacterial mechanism of resistance to chloramphenicol?
-enzymatic inactivation
How do oxazolidinones work?
-Binds 50S subunit and prevents association with 30S subunit
What antibiotic classes inhibit bacterial folic acid metabolism?
- Sulfonamides
- Trimethoprim
How do sulfonamides work?
- inhibit bacterial purine/pryimidine synthesis
- blocks dihydropteroate synthetase
How does trimethoprim work?
- inhibits bacterial purine/pyrimidine synthesis
- inhibits DHFR
How is bacterial resistance of sulfonamides mediated?
By pass the blocked pathway
How is bacterial resistance of trimethoprim mediated?
Bypass the blocked pathway
What class of antibiotics are nucleic acid synthesis inhibitors?
- Quinolones
- Rifampicin
How do quinolones work?
-block DNA gyrase
& topoisomerase IV
How is bacterial resistance to quinolones mediated?
- mutations in gyrase and topo IV genes is the most common mechanism of resistance
- Efflux
- Qnr produced and binds/protects DNA gyrase
How does rifampicin work?
Blocks beta-subunit of the bacterial RNA polymerase enzyme
How is bacterial resistance to rifampicin mediated?
mutations in the gene for the beta-subunit of RNA Polymerase
What antibiotics work via bacterial membrane disruption?
- Polymixins
- Daptomycin
How do polymixins work?
-act like a detergent and disrupt cytoplasmic membrane
*used topically due to toxicity
*resistance is rare
How does Daptomycin work?
- dysrupts cell membrane
- Depolarizes bacteria resulting in bacterial death from release of intracellular ions
Combinations of penicillins and ____________ because penicillins allow increased passage of __________.
aminoglycosides
