- A heteropolymer of glycan chains cross-linked by amino acids - Unique to bacteria
Is peptidoglycan found in all bacteria? Is it found in animal or plant cells?
- No, almost all, but not mycoplasma - Not found in animal or plant cells
Name the amino acid sugar components of peptidoglycan. Describe the structure of the chain
- The sugars: MurNac, GlcNac (a repeating disaccharide w/ beta 1,4 linkage) - The disaccharide has a tetrapeptide side chain - The peptide side chains are crossed linked together through a pentaglycine bridge between two disaccharide units.
Describe the differences in structure of the cell envelope in Gram positive and Gram Negative bacteria
Gram +: May have a capsule, protein, teichoic acids, polysaccharides, etc. on outside, then a thick cell wall (peptidoglycan), then a cytoplasmic membrane Gram -: May have a capsule, then outer membrane, then small peptidoglycan cell wall, then cytoplasmic membrane
What is the Park nucleotide? How is this different in Gram - bacteria?
- The MurNac pentapeptide - MurNac- UDP w/ L-ALA--D-Glu--L-LYS--D-ALA--D-ALA - In Gram - , the pentapeptide is MurNac w/ ALA--GLU--DAP--ALA--ALA
How are the cross links between the peptide side chains different in Gram - and Gram + bacteria?
- In gram + bacteria, the L-LYS in one peptide chain is attached to the fourth amino acid (D-ALA) of another peptide chain through a pentaglycine bride
- In gram - bacteria, the DAP of one peptide chain is bound to the fourth D-ALA of another chain
How is UDP-MurNAc synthesized?
UDP-GlcNAc + Phosophoenol pyruvate (PEP) → UDP-GlcNAc enolpyruvate → UDP-MurNAc - pyruvyl transferase is the main enzyme involved in this process
How does Fosfomycin interrupt cell wall synthesis?
- Fosfomycin is a structural analog of phosphoenolpyruvate (PEP) - It binds covalently to the active site of the pyruvyl transferase, which prevents the synthesis of UDP-MurNAc from UDP-GlcNAc
Describe the synthesis of UDP-MurNAc-Pentapeptide
- Sequential addition of L-Ala, D-Glu, and L-Lys by synthases (non-ribosomal) - Then two L-Ala are converted to D-Ala (Racemase enzyme catalyzes this rxn) - Then the two D-Ala amino acids form a dipeptide with the help of Ligase - Finally, the D-Ala--D-Ala dipeptide is added to L-Lys --now, there are 5 amino acids
How does D-Cycloserine inhibit cell wall synthesis?
- D-Cycloserine is a structural analog of D-Ala. - It acts as a competitive inhibitor of both alanine racemase (which converts L-Ala to D-Ala) and ligase (which binds the two D-Ala amino acids together) - Therefore, D-Cycloserine interferes w/ the production of the pentapeptide side chain.
Describe the 6 Membrane-bound Steps of Peptidoglycan Synthesis
1. Addition of the Glycosyl Carrier Lipid (GCL) to Pentapeptide MurNAc; GCL is the cytoplasmic membrane anchor 2. Addition of GlcNAc and flipping of unit across to extracellular space 3 &4. Addition of pentaglycine bridge to L-Lys using ATP energy 5. Transglycosylation - connecting two disaccharide units together 6. Regeneration of GCL-P
What occurs during the transpeptidation step of peptidoglycan synthesis in Gram + bacteria?
The pentaglycine bridge of one pentapeptide binds to fourth amino acid (D-Ala) of another disaccharide sugar. The fifth amino acid (D-Ala) is released from the side chain.
How does Vancomycin inhibit cell wall synthesis in Gram + bacteria?
- It binds to the terminal D-Ala--D-Ala residues of the pentapeptide side chain, which occurs on the outer face of cytoplasmic membrane. - This binding prevents the precursor (disaccharide GlcNAc-MurNAc unit) from binding the the synthase, which would lead to transglycosylation otherwise
Which transposon encodes VanA-type resistance?
What happens during VanA-type resistance?
This is characterized by inducible high levels of resistance to vancomycin and teicoplanin. A substitution of D-Ala--D-Lac for normal D-Ala--D-Ala in peptidoglycan synthesis occurs. This decreases the affinity of the molecule for glycopeptides and leads to vancomycin resistance.
How does Bacitracin affect cell wall synthesis?
It blocks the regeneration of GCL-P
How do β-lactam Antibiotics inhibit transpeptidation?
- β-lactams are substrate analogs for the terminal D-Ala--D-Ala--COOH region of pentapeptide - They bind transpeptidases (also known as penicillin binding proteins [PBPs]), which are responsible for catalyzing the formation of the peptide bonds btwn the Pentaglycine bridge and D-Ala
Which part of cell wall synthesis do β-lactams interrupt?
Transpeptidation - connection of pentaglycine bridge of one disaccharide unit with a D-Ala of another peptide side chain
Is penicillin bacteriocidal or bacteriostatic?
Bacteriocidal on actively growing bacteria. Cause cells to lyse due uninhibited cell growth in a cell with structural degradation of cell wall caused by penicillin.
What is β-Lactamase?
- a bacterial enzyme that destroys penicillin before it comes into contact with the cell surface. - Gram + bacteria often make these enzymes in large amts after induction by corresponding antibiotic. - Gene coding is on a transposon, which hops to another strain
Which gene is encodes for the restructuring of PBP to PBP2?
mecA gene PBP is required for entry of antibiotic into bacterial cell.
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