Bacterial Cell Wall Synthesis and Penicillin Mechanism
Concept Name
Bacterial Cell Wall Synthesis
Genetic Loci
mecA (SCCmec cassette in MRSA) encodes PBP2a – methicillin resistance. pbp genes (multiple loci) encode penicillin‑binding proteins in E. coli.
Intracellular Cascade
Peptidoglycan synthesis: UDP‑NAG and UDP‑NAM are assembled in the cytoplasm → bactoprenol transports subunits across the membrane → transglycosylase polymerizes glycan chains → transpeptidase (PBP) cross‑links peptides. Autolysins remodel the wall during growth.
Required Cofactors
Mg²⁺ and Mn²⁺ are required for transpeptidase activity. ATP is required for synthesis of precursors.
Histology Stains
Gram stain differentiates bacteria based on cell wall thickness: Gram‑positive (thick peptidoglycan) stain purple; Gram‑negative (thin peptidoglycan + outer membrane) stain pink.
EM Findings
Gram‑positive bacteria show a thick, dense peptidoglycan layer (20‑80 nm). Gram‑negative bacteria have a thin peptidoglycan layer (5‑10 nm) between inner and outer membranes.
Knockout Phenotype
Conditional knockout of PBP1a in S. aureus leads to defective cell wall synthesis and rapid lysis. mecA expression confers β‑lactam resistance.
Specific Toxins
Penicillin binds irreversibly to PBPs, blocking transpeptidation. Vancomycin binds D‑Ala‑D‑Ala terminus of peptidoglycan precursors. Lysozyme cleaves the β‑1,4‑glycosidic bond between NAG and NAM.