Penicillin-Binding Protein 5/6 Acting as a Decoy Target in Pseudomonas aeruginosa Identified by Whole-Cell Receptor Binding and Quantitative Systems Pharmacology.

The β-lactam antibiotics have been successfully used for decades to combat susceptible Pseudomonas aeruginosa, which has a notoriously difficult to penetrate outer membrane (OM). However, there is a dearth of data on target site penetration and covalent binding of penicillin-binding proteins (PBP) for β-lactams and β-lactamase inhibitors in intact bacteria. We aimed to determine the time course of PBP binding in intact and lysed cells and estimate the target site penetration and PBP access for 15 compounds in P.

Penicillin-Binding Protein Occupancy Dataset for 18 β-Lactams and 4 β-Lactamase Inhibitors in Neisseria gonorrhoeae.

The lack of effective first-line antibiotic treatments against Neisseria gonorrhoeae, and the worldwide dissemination of resistant strains, are the main drivers of a worsening global health crisis. β-lactam antibiotics have been the backbone of therapeutic armamentarium against gonococci. However, we are lacking critical insights to design rationally optimized therapies.

PBP Target Profiling by β-Lactam and β-Lactamase Inhibitors in Intact Pseudomonas aeruginosa: Effects of the Intrinsic and Acquired Resistance Determinants on the Periplasmic Drug Availability.

The lack of effective treatment options against Pseudomonas aeruginosa is one of the main contributors to the silent pandemic. Many antibiotics are ineffective against resistant isolates due to poor target site penetration, efflux, or β-lactamase hydrolysis. Critical insights to design optimized antimicrobial therapies and support translational drug development are needed.

Molecular Basis of AmpC β-Lactamase Induction by Avibactam in : PBP Occupancy, Live Cell Binding Dynamics and Impact on Resistant Clinical Isolates Harboring PDC-X Variants.

Avibactam belongs to the new class of diazabicyclooctane β-lactamase inhibitors. Its inhibitory spectrum includes class A, C and D enzymes, including AmpC. Nonetheless, recent reports have revealed strain-dependent avibactam AmpC induction.

Species Diversity Along the Danube River Assessed by Gene Sequence and MALDI-TOF MS Analyses of Cultivated Strains.

A collection of 611 isolated from 14 sampling sites along the Danube River were identified previously by MALDI-TOF MS with the VITEK MS system and were grouped in 53 clusters by their main protein profiles. The strains were identified in the present study at the phylospecies level by gene sequencing. Partial sequences of the gene of 190 isolates representatives of all clusters were analyzed.

Effective ventilation at conventional rates with tidal volume below instrumental dead space: a bench study.

Objective: The authors previously showed that 48% of infants <800 g were ventilated with tidal volume (VT) < dead space (DS) using volume guarantee (VG) ventilation. Here, The authors sought to confirm those findings under the rigorous conditions of a bench study.

Design And Methods: The authors measured the time to wash out CO2 from a 45-ml test lung using end-tidal CO(2) monitor (ETCO(2)).