Project description:Using in vitro directed evolution, we show that mismatch repair-deficient Pseudomonas aeruginosa can engage novel resistance mechanisms to ceftazidime-avibactam.
Project description:The periplasm of gram-negative bacteria facilitates critical functions, including nutrient uptake, cell wall metabolism, antibiotic resistance, and virulence. Efficient quality control of proteins involved in these processes is crucial for bacterial fitness and survival. The limited size of the periplasm has hindered high-resolution mechanistic investigations of complex processes within this compartment. Using in-cell NMR spectroscopy, we dissected the mechanism of periplasmic quality control of the metallo-β-lactamase NDM-1 under conditions of zinc starvation, which destabilizes its native structure promoting its degradation. We show that the protease Prc targets membrane-bound NDM-1 at specific residues and secondary structure motifs, while DegP processes peptides generated by Prc. This approach discloses the concerted mechanism of these proteases at atomic resolution in the periplasm of live cells.
2025-07-10 | PXD065625 | Pride
Project description:Metallo-beta-lactamase-producing Pseudomonas aeruginosa in Switzerland
Project description:Emergence of Ceftazidime-Avibactam resistant KPC-producing K. pneumoniae (KPC-Kp) during ceftazidime-avibactam-based antimicrobial treatment.
Project description:Optimal Ceftazidime/Avibactam Dosing Exposure against KPC-producing Klebsiella pneumoniae
| PRJNA836572 | ENA
Project description:Ceftazidime-Avibactam Resistance Development following Ceftazidime-Avibactam-based therapy in critically-ill patients with infections caused by KPC-producing Klebsiella pneumoniae