Antibiotics I - Med Micro Flashcards
The role of Penicillin Binding Proteins and the Cell wall
PBPs are needed in order for cross linking and building the peptidoglycan cell wall. Act as transglycosylases and transpeptidases. Cell wal agents act on specific PBPs
transglycosylases
PBPs act as these in joining NAG and NAM
transpeptidases
PBPs act as these in the cross linking of the peptidoglycan sheets- it will cleave off the final D-ala residue for cross linking to occur
B Lactam Antibiotics AND the Classes
Are B Lactam Cell Wall Agents, because they inhibit cell wall synthesis. They consist of Penicillins, Cephalosporins, Carbapenems and Monobactams ( Aztreonam)
Pathways utilized by B lactam antibiotics into the outer membrane of gram negative bacteria
- a lipid mediated pathway for hydrophobic antibiotics 2. general diffusion porins for hydrophilic antibiotics
What are Penicillins and what do they do?
are B lactam based compounds, have a 4 membered B lactam ring and a 5 membered thiazolidine ring its fused to.
Features of the B lactam ring
- it binds to and inhibits transpeptidases (PBPs), 2. it is a substrate for B lactamases 3. it is a very unstable structure
What are Cephalosporins and what do they do?
are described in context of generations, Are structurally similar to penicillins. Have increasing activity to various gram negative bacteria. Higher generations are less susceptible to Beta lactamases
The other Inhibitors of Cell Wall Synthesis
Carbapenem and Monobactams
How do the Beta Lactam Antibiotics work?
B Lactam Antibiotics are structurally similar to the D-ala-D-ala residue so B lactam antibiotics react/bind to PBP proteins and inactivate them
How does the Bacteria FIGHT back? What’s in its arsenal?
B- lactamases, ESBLs (extended spectrum B lactamases), Amp C Beta Lactamases (IDBLs) and the Carbapenemases
What are the B Lactamases and how do they work?
Are bacterial enzymes that can inactivate the B Lactam antibiotics by hydrolyzing the B lactam bond and destroying the B Lactam ring. Are a form of resistance to the antibiotics. Can differ in their substrate profile
B Lactamase Production
May be constitutive- a constant basal level of the enzyme is produced at all times, not affected by external env’t or inducible - produced after exposure to certain antibiotics in its env’t
Activity of the B lactamase depends on
Depends on having a zinc or a serine at the active site to hydrolyze the B lactam ring
Different Classes of B lactamases
- Narrow Spectrum B Lactamases 2. Extended Spectrum Beta Lactamases (ESBLs) 3. AmpC production (IDBL) 4. Carbapenemase production (CRE)