Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.

Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.

G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at their orthosteric binding site. Despite their prominence, predicting the pharmacological effects of novel GPCR-targeting drugs remains challenging due to the complex functional dynamics of these receptors.

Nosocomial outbreak due to a novel sequence type of carbapenem-resistant Acinetobacter seifertii.

Background: Acinetobacter seifertii, a member of A baumannii-calcoaceticus complex, can be considered a pathogen of concern due to the presence of resistance genes. The aim of the study was to describe an outbreak of carbapenem-resistant A seifertii among neonates admitted to the neonatal intensive care unit (NICU) at a tertiary care hospital.

Methods: All patients with carbapenem-resistant A seifertii diagnosed and admitted to the NICU from June 2023 to October 2023 were included.

Ceftazidime-avibactam tolerance and persistence among difficult-to-treat KPC-producing Klebsiella pneumoniae clinical isolates from bloodstream infections.

Purpose: Tolerance and persistence occur "silently" in bacteria categorized as susceptible by antimicrobial susceptibility testing in clinical microbiology laboratories. They are different from resistance phenomena, not well-studied, and often remain unnoticeable. We aimed to investigate and characterize ceftazidime-avibactam (CZA) tolerance/persistence in 80 Klebsiella pneumoniae isolates from bloodstream infections.

Metabolic Reprogramming of Exposed to Serum and Its Potential Implications in Host Immune System Evasion and Resistance.

The aim of this study was to identify, using proteomics, the molecular alterations caused by human serum exposure to ACH2. The analysis was performed under two different conditions, native serum from healthy donors and heat-inactivated serum (to inactivate the complement system), and at two different times, after 1 and 4 h of serum exposure. More than 1,000 bacterial proteins were identified at each time point.