A5059440101- Antibiotic Resistance in Bacteria
- Bacterial biofilms and quorum sensing
- Antibiotics Pharmacokinetics and Efficacy
- Tuberculosis Research and Epidemiology
- Antimicrobial Peptides and Activities
- Pneumocystis jirovecii pneumonia detection and treatment
- Protein Tyrosine Phosphatases
- Cellular Mechanics and Interactions
- Mycobacterium research and diagnosis
- Immune Cell Function and Interaction
- Microtubule and mitosis dynamics
- Antibiotic Use and Resistance
- Glycosylation and Glycoproteins Research
- Erythrocyte Function and Pathophysiology
- Hippo pathway signaling and YAP/TAZ
- Computational Drug Discovery Methods
- Biosimilars and Bioanalytical Methods
- Cell Adhesion Molecules Research
- Pharmaceutical and Antibiotic Environmental Impacts
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Galectins and Cancer Biology
- Machine Learning in Bioinformatics
Institut de Pharmacologie et de Biologie Structurale
2005-2008
Centre National de la Recherche Scientifique
2005
ABSTRACT Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent and have become a major worldwide threat to human health. Carbapenem resistance is driven primarily the acquisition of β-lactamase enzymes, which able degrade carbapenem antibiotics (hence termed carbapenemases) result in high levels treatment failure. Clinically relevant carbapenemases include both serine β-lactamases (SBLs; e.g., KPC-2 OXA-48) metallo-β-lactamases (MBLs), such as NDM-1....
Haematopoietic cell kinase (Hck) is a protein tyrosine of the Src family specifically expressed in phagocytes as two isoforms, p59Hck and p61Hck, present at plasma membrane lysosomes, respectively. We report that ectopic expression constitutively active mutant p61Hck (p61Hck ca ) triggered de novo formation actin‐rich rings ventral face cells we characterized bona fide podosome rosettes, structures involved migration. Their required adaptor domains activity integrity microfilament...
The clinical effectiveness of carbapenem antibiotics such as meropenem is becoming increasingly compromised by the spread both metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) enzymes on mobile genetic elements, stimulating research to find new β-lactamase inhibitors be used in conjunction with carbapenems other β-lactam antibiotics. Herein, we describe our initial exploration a novel chemical series inhibitors, from concept efficacy, survival model using an advanced tool compound...
LasB elastase is a broad-spectrum exoprotease and key virulence factor of Pseudomonas aeruginosa, major pathogen causing lung damage inflammation in acute chronic respiratory infections. Here, we describe the chemical optimization specific inhibitors with druglike properties investigate their impact cellular animal models P. aeruginosa infection. Competitive inhibition was demonstrated through structural kinetic studies. In vitro confirmed respect to several host target proteins, namely,...
The clinical effectiveness of the important β-lactam class antibiotics is under threat by emergence resistance, mostly due to production acquired serine- (SBL) and metallo-β-lactamase (MBL) enzymes. To address this resistance issue, multiple β-lactam/β-lactamase inhibitor combinations have been successfully introduced into clinic over past several decades. However, all those contain SBL inhibitors and, as yet, there are no MBL in use. Consequently, exists an unaddressed yet growing...
Chronic infection by Pseudomonas aeruginosa in cystic fibrosis (CF) patients is a major contributor to progressive lung damage and poorly treated available antibiotic therapy. An alternative approach the development of additional treatments identify complementary therapies which target bacterial virulence factors necessary for establishment and/or maintenance chronic infection. The P. elastase (LasB) has been suggested as an attractive anti-virulence due its extracellular location, harmful...
The diazabicyclooctanes (DBOs) are a class of serine β-lactamase (SBL) inhibitors that use strained urea moiety as the warhead to react with active residue in site SBLs. first in-class drug, avibactam, well several other recently approved DBOs (e.g., relebactam) or those clinical development nacubactam and zidebactam) potentiate activity β-lactam antibiotics, various extents, against carbapenem-resistant Enterobacterales (CRE) carrying A, C, D SBLs; however, none these able rescue...
ANT3310 is a novel broad-spectrum diazabicyclooctane serine β-lactamase inhibitor being developed in combination with meropenem (MEM) for the treatment of serious infections hospitalized patients where carbapenem-resistant Gram-negative pathogens are expected. In this study, we evaluated
Novel therapies are required to treat chronic bacterial infections in cystic fibrosis (CF) sufferers. The most common pathogen responsible for these is Pseudomonas aeruginosa, which persists within the lungs of CF sufferers despite intensive antibiotic treatment. P. aeruginosa elastase (also known as LasB or pseudolysin) a key virulence determinant that contributes pathogenesis and persistence patients. crucial role pseudomonal makes it good target development an adjuvant drug Herein we...