Lec2 Antibiotic Strategies Flashcards
What are the four main classes of antibiotics?
inhibitors of
- peptidoglycan [cell wall] synthesis
- protein synthesis
- polymerase activity
- folic acid metabolism
What are 4 main beta-lactam antibiotics that affect peptidoglycan synthesis?
- penicillin
- cephalosporin
- carbapenems
- monobactam
Where does penicillin come from?
- penicillium mold
Are gram + or - more affected by penicillin?
gram + because there is only one lipid bilayer to get through
How does penicillin work?
prevents synthesis of peptidoglycan cell wall by inhibiting transpeptidase that participates in cross-linking between parallel strands of murein
What is transpeptidase? Why is it significant?
an enzyme in bacterial cell wall that makes peptide cross-linking bonds to synthesize peptidoglycan
- it is inhibited by penicillin
What is significant in penicillin structure?
- contains beta-lactam ring = internal peptide bond
- contains two alanines within structure
- mimics substrate structure so feeds into transpeptidase active site and blocks it
What are 3 important beta lactams?
- penicillin
- cephalosporin
Cephamycin
What is beta-lactamase?
- enzyme that makes bacteria resistant to beta lactams [aka penicillin, cephamycin, cephalosporin]
- hydrolyzes the antibiotic beta-lactam structure
How do bacteria develop resistance?
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
What are two drugs that affect peptidoglycan synthesis?
vancomycin
bacitracin
What is mech of vancomycin?
recognizes ala and inhibits polymerization of peptidoglycan
What are two strategies of bacterial resistance to vancomycin?
strategy 1: decrease penetration of antibiotic to its target
strategy 2: alter target of antibiotic
What is significance of bacteria decreasing penetration of vancomycin?
- gram negative bacteria intrinsically resistant because vancomycin cannot get across outer membrane
What is mech of vancomysin resistance? which bacteria commonly have this?
- 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
What are 3 types of antibiotics that affect membrane of cell wall?
- polymyxins [cationic (+) detergents]
- polyene antibiotics [amphotericine B bind to sterols]
- azoles [inhibit cholesterol synthesis]
What is name for fungizone?
amphotericine B
What are 7 antibiotics that affect protein synthesis?
- aminoglycosides
- tetracyclins
- cholramphenicol
- macrolides [erythromycin]
- linezolid
- streptogramins
- clindamycin
What is mech of aminoglycoside action? What are the 3 mechs of resistance?
- affect protein synthesis
1. decreased penetration of antibiotic to target
2. alters target of antibiotic
3. inactivates antibiotic [MAIN MECH] by changing structure
What is mech of tetracyclin action? What is mech of resistance?
- affect protein synthesis
- transport of antibiotic out of cell
What is mech of chloramphenicol action? What is mech of resistance?
- affect protein synthesis
- by acetyl-transferase CAT
What is mech of macrolides [erythromycin] action? What is mech of resistance?
- affect protein synthesis
- alters 50s ribosomal proteins, methylation of 23s RNA
What is mech of linezolid action? What is mech of resistance?
- affect protein synthesis
- changes 23s RNA
What is mech of stretogramin action? What is mech of resistance?
- affect protein synthesis
- efflux, modifies/inactivates target
