Staphylococcus aureus is a major human and veterinary pathogen worldwide. Methicillin-resistant S. aureus (MRSA) poses a significant and enduring problem to the treatment of infection by such strains. Resistance is usually conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a), with significantly lower affinity for β-lactams. This resistance allows cell-w...

This review covers the uses of fluorescence polarization and anisotropy for the investigation of bacterial penicillin binding proteins (PBPs), which are the targets of β-lactam antibacterial drugs (penicillins, cephalosporins, carbapenems, and monobactams), and of the β-lactamase enzymes that destroy these drugs and help to render bacterial pathogens resistant to them. Fluorescence polarization...

Induction of ampC β-lactamase expression can often compromise antibiotic treatment and is triggered by several β-lactams (such as cefoxitin and imipenem) and by the β-lactamase inhibitor clavulanic acid. The novel β-lactamase inhibitor avibactam (NXL104) is a potent inhibitor of both class A and class C enzymes. The potential of avibactam for induction of ampC expression in Enterobacter cloacae...

Resistance to β-lactams is constantly increasing due to the emergence of totally new enzymes but also to the evolution of preexisting β-lactamases. GES-1 is a clinically relevant extended-spectrum β-lactamase (ESBL) that hydrolyzes penicillins and broad-spectrum cephalosporins but spares monobactams and carbapenems. However, several GES-1 variants (i.e., GES-2 and GES-5) previously identified a...

AmpC β-lactamases are enzymes that resistant to β-lactams, such as penicillin and cephalosporin, but not cefoxitin cefotetan. This study was conducted characterize in Enterobacteriaceae. included 200 cephalosporin-resistant Gram-negative isolates recovered from different samples between January 2015 December 2016. The were subjected phenotypic tests, those tested positive further analyzed by PC...

This review covers the uses of fluorescence polarization and anisotropy for the investigation of bacterial penicillin binding proteins (PBPs), which are the targets of β-lactam antibacterial drugs (penicillins, cephalosporins, carbapenems, and monobactams), and of the β-lactamase enzymes that destroy these drugs and help to render bacterial pathogens resistant to them. Fluorescence polarization...

The stereoselectivity of the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents was investigated experimentally by determination of the product stereochemistry and theoretically via DFT calculations. The results indicate that imines preferentially attack the less sterically hindered exo-side of the ketenes to generate zwitterionic intermediates. Subsequen...

β-Lactamase-mediated resistance is a growing threat to the continued use of β-lactam antibiotics. The use of the β-lactam-based serine-β-lactamase (SBL) inhibitors clavulanic acid, sulbactam, and tazobactam and, more recently, the non-β-lactam inhibitor avibactam has extended the utility of β-lactams against bacterial infections demonstrating resistance via these enzymes. These molecules are, h...

The structural motif of α,α-difluoro-substituted carboxyl and carbonyl groups with hydroxy- or amino-substituents at the stereogenic carbon in β-position is found frequently drugs biologically active compounds. A straightforward method for obtaining those targets high enantiomeric purity given by asymmetric difluoro-Reformatsky imino-difluoro-Reformatsky reactions that lead to α,α-difluorinated...

The emergence of Klebsiella pneumoniae carbapenemases (KPCs), β-lactamases that inactivate "last-line" antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ) and avibactam (AVI), a potent β-lactamase inhibitor, represents an attempt to overcome this formidable threat and to restore the efficacy of the antibiotic agai...