Bacterial Structure - Lec 3, 4, 5 PDF

 Biosynthesis of PDG 1/3/2025 21 Biosynthesis of PDG and Antibiotics That Act on PDG ❑All antibiotics that inhibit cell wall synthesis are bactericidal ❑NAG/NAM-pentapeptide Synthesis takes place in cytosol ❑Phosphoenolpyruvate (PFP)  NAM via transferase ✓Fosfomycin is an inhi...

 Biosynthesis of PDG 1/3/2025 21 Biosynthesis of PDG and Antibiotics That Act on PDG ❑All antibiotics that inhibit cell wall synthesis are bactericidal ❑NAG/NAM-pentapeptide Synthesis takes place in cytosol ❑Phosphoenolpyruvate (PFP)  NAM via transferase ✓Fosfomycin is an inhibitor of the MurA enzyme (UDP-N- acetylglucosamine-enolpyruvyltransferase) ✓L-alanine  D-alanine via Alanine racemase ❑2 D-alanine is converted to D-Alanyl D-Alanine via D-Ala D-Ala synthetase ✓D-Cycloserine inhibits both enzymes ❑Bactoprenol transports NAG/NAM-P ✓Bacitracin inhibits this transport 1/3/2025 22 Biosynthesis of PDG and Antibiotics That Act on PDG ❑Autolysins break β-(1-4) glyosidic bonds of PDG ❑NAG/NAM-P is inserted into the old PDG ❑Transglycosidase catalyzes formation of glyosidic bond ❑This is the second step of biosynthesis of PDG ✓Vancomycin inhibits Transglycosidase ❑Transpeptidase (PBP) reforms peptide cross-links between rows and layers of PDG to make a wall strong ❑This is the final step of biosynthesis of PDG ✓β-lactams inhibit Transpeptidase ✓Vancomycin binds to the D-Ala-D-Ala and prevents binding to PBP ✓Both prevent cross-linking 1/3/2025 23 3. TEICHOIC ACIDS (TA) ❑Associated with Gram positive bacteria ONLY ❑50% of the weight of the cell wall ❑Cell surface anionic glycopolymers ❑Responsible for negative charge ❑Highly immunogenic ❑Mediate adherence to mucosal cells 1/3/2025 24 3. TEICHOIC ACIDS (TA) ❑Two types of TAs A.WTAs divided into 2 components 1.Disaccharide unit (linkage unit): ❑N-acetylmannosamine & NAG-1-phosphate connected by β-(1,4)-glycosidic bond ❑NAG of Disaccharide unit is covalently linked to 6- OH of NAM in PDG 1/3/2025 25 TYPES OF TEICHOIC ACIDS (WALL- AND LIPO-TEICHOACIDS) 2. Main chain polymer: ❑ 40-60 unit of glycerol or ribitol joined via phosphodiester bond & carrying D-alanine, NAG or glucose substituent B.LTA is linked to cytoplasmic membrane with glycolipid anchor ❑glycolipid anchor is disaccharide unit of glucose connected by β- (1,6)-glycosidic bond with diacylglycerol ❑Function of WTA: Cell shape determination, cell division regulation, pathogenesis, antibiotic resistance ❑Function of LTA: Protection against cationic antimicrobial peptide 1/3/2025 26 1/3/2025 27  FUNCTIONS OF THE CELL WALL ❑Determining and Maintaining cell's shape ❑Countering the effects of osmotic pressure & prevent cell lysis ❑Providing attachment sites for bacteriophages ❑Providing a rigid platform for surface appendages- flagella, fimbriae & pili all originate from the wall and extend beyond it ❑Play an essential role in cell division ❑Site of major antigenic determinants of the cell surface ❑Resistance of Antibiotics 1/3/2025 28