Micro B-8 Antibiotics That Affect Cell Wall Synthesis

Front 1

Why is Bacterial Cell Wall Synthesis Important to the bacterium?

Back 1

- Protects the bacteria from osmotic shock (from within and without)
- Maintains the shape of the bacteria- Assists in cell division

Front 2

Why is Bacterial Cell Wall Synthesis Important to you?

Back 2

- Most bacteria possess a peptidoglycan layer
- The unique chemistry of bacterial cell walls makes the enzymes in their synthesis ideal targets for antibiotics

Front 3

What is Peptidoglycan?
Function?
What bacteria is the only one that doesn’t have PG?

Back 3

- Peptidoglycan (PG) is a heteropolymer of glycan chains cross-linked by amino acids
- Helps bacteria resist osmotic stress, determines cell shape, cell division, mediates bacterial-host interactions
- mycoplasma and some marine halophiles

Front 4

How is the cell envelope for gram pos and neg different?

Back 4

- Gram pos has a thicker peptidoglycan, which is between capsule and cytoplasmic memb
- Gram neg has thinner peptidoglycan, which is between outer membrane and cytoplasmic memb
- Gram pos has no outer memb

Front 5

What is the repeating disaccharide seen in peptidoglycan?
Where on the repeating dissacharide do sidechains attach?

Back 5

- B-1,4-linkage of MurNAc and GlcNAc
- MurNAc

Front 6

What is the peptidoglycan cross link between repeating dissacharides in gram positives?

Back 6

- The sidechain Lys from one repeating disaccharide to sidechain Ala of next one, connected by pentaglycine

Front 7

How do repeating disaccharide chains connect in gram negatives?

Back 7

- Sidechain meso-Diaminopimelic acid (DAP) of one repeating dissacharide crosslinks to ALA of next one

Front 8

What is a park nucleotide?

Back 8

- A MurNAc pentapeptide that is precursor to peptidoglycan cell wall: Ala-Glu-Lys-Ala-Ala

Front 9

How does the cytoplasmic steps of peptidoglycan synthesis?

Back 9

- UDP-GlcNAc + PEP → UDP-GlcNAc enolpyruvate → UDP-MurNAc (has tripeptide)
- L-Ala -> D-Ala
- D-Ala + D-Ala -> D-Ala-D-Ala
- D-Ala-D-Ala + UDP-MurNAc -> UDP-MurNAc-pentapeptide

Front 10

MOA of fosfomycin?

Back 10

- structural analog of phosphoenolpyruvate -> Binds covalently to the active site of the pyruvyl transferase -> blocks (UDP-GlcNAc + PEP → UDP-GlcNAc enolpyruvate)

Front 11

How does synthesis of UDP-MurNAc-Pentapeptide occur in gram positives?

Back 11

- Mur Synthases allow sequential addition of L-Ala, D-Glu and L-Lys

Front 12

MOA of D-cycloserine?

Back 12

- Structural analog of D-alanine -> competitively inhibit both alanine racemase (L-Ala -> D-Ala) and D-alanine ligase (D-Ala + D-Ala -> D-Ala-D-Ala)

Front 13

What are the membrane-bound steps in peptidoglycan synthesis?

Back 13

- Step 1: GCL-P + UDP-MurNAc -> UMP + GCL-PP-MurNAc (Glycosyl Carrier Lipid Pentapeptide MurNAc)
The first membrane-bound intermediate in PG synthesis (step 1)
- Step 2: Addition of GlcNAc: GlcNAc-MurNac-PP-GCL
- Steps 3,4: Synthesis of Pentaglycine Bridge
- Step 5: Transglycosylation (attachment of repeating dissacharides
- Step 6: Regeneration of GCL-P
- Step 7: Transpeptidation

Front 14

MOA of vancomycin?

Back 14

- binds terminal D-Ala-D-Ala residues of pentapeptide on outer face of cytoplasmic membrane -> prevents precursor unit from binding to the synthase -> inhib transglycosylation (combining the repeating disaccharides)

Front 15

MOA of bacitracin?

Back 15

- Inhibits regeneration of GCL-P (GCL-PP -> GCL-P)

Front 16

What are the B-lactam antibiotics? MOA of β-lactam Antibiotics?

Back 16

- penicillin, cephalosporin
- β-lactams are substrate analogs of the terminal D-ala-D-ala-COOH region of the pentapeptide -> therefore they bind to transpeptidases -> inhib transpeptidation