Ceftazidime

Bacterial cell wall synthesis is essential for maintaining bacterial structural integrity and viability. Penicillin-binding protein 3 (PBP3) is a key transpeptidase that catalyzes the cross-linking of peptidoglycan strands, a critical step in cell wall assembly. Disruption of this process compromises the cell wall, leading to osmotic imbalance and bacterial lysis.
Ceftazidime acts as a mechanism-based inhibitor that covalently binds to the active site of PBP3. As shown in the crystal structur, ceftazidime forms an irreversible covalent linkage with Ser294 in the PBP3 active site, permanently blocking its transpeptidase activity. This covalent modification prevents peptidoglycan cross-linking, resulting in the loss of cell wall integrity and ultimately bacterial cell death. This structural evidence provides a molecular basis for the potent antibacterial activity of ceftazidime against susceptible Gram-negative pathogens.
The mechanism of its antibacterial effect is:
• Covalently binding to Ser294 in the active site of PBP3
• Irreversibly inhibiting transpeptidase activity
• Blocking peptidoglycan cross-linking and cell wall synthesis
• Disrupting cell wall integrity, leading to osmotic lysis and bacterial death

Fig. 1 Ribbon representation of PBP3 bound to ceftazidime.(Sainsbury S.; et al. 2011)

Hu X et al. developed a photochromic glycomicelle system loaded with ceftazidime to enable superresolution imaging of antibiotic-induced bacterial structural disruption. The targeted adhesion of glycomicelles to Pseudomonas aeruginosa through multivalent galactose–Lec A interactions and the subsequent light-triggered release of the payload were investigated in vitro. This system allows for the on-demand release of ceftazidime via UV irradiation, facilitating the in situ visualization of its antibacterial action at the single-cell level. Using STORM superresolution microscopy, this approach can track the dynamic morphological changes of bacteria in response to ceftazidime treatment. Compared with conventional genomic and proteomic methods that require cell lysis, this imaging system permits the real-time observation of how ceftazidime disrupts bacterial structural integrity. This research provides a high-precision chemical tool for studying antibiotic mechanisms of action in situ and offers a theoretical basis for the potential application of photochromic glycomicelles in antibacterial drug evaluation.

Fig. 2 Schematic illustration of the photochromic glycomicelle-based system for superresolution imaging of ceftazidime-induced bacterial structural disruption (Hu X.; et al. 2024)