Penicillin and related beta-lactams comprise one of our oldest and most widely used antibiotic therapies. These drugs have long been known to target enzymes called penicillin-binding proteins (PBPs) that build the bacterial cell wall. Investigating the downstream consequences of target inhibition and how they contribute to the lethal action of these important drugs, we demonstrate that beta-lac...

The mechanism of action of a new orally active cephalosporin, FK027, was compared to that of cephalexin and cefaclor to elucidate its excellent antibacterial activity against Gram-negative bacteria. FK027 showed very high affinity for the penicillin-binding proteins (PBPs) 3, 1a and 1bs of Escherichia coli whereas cephalexin showed fairly high affinity for PBPs 1a, 4 and 3. The ability of FK027...

One of the joys of science is seeing old problems solved. Just as satisfying is the pleasure of seeing long-unanswered questions revitalized by the application of new technologies or simply by someone reinvestigating the problem with fresh eyes. In this issue, Joseleau-Petit et al. (5) provide us the opportunity to share this second kind of enjoyment by resurrecting the rather moribund subject ...

The beta-lactam antibiotics are the most widely used of all the groups of antimicrobials, but beta-lactam resistance is increasingly common among members of the Bacteroides fragilis group. Three major mechanisms are involved in beta-lactam resistance, and they act together in certain instances. In the present study, 2 resistant mutants (238m and 1186m) of Bacteroides thetaiotaomicron, obtained ...

Beta-lactam antibiotics sensitize Enterococcus faecium to killing by endogenous antimicrobial peptides (AMPs) of the innate immune system and daptomycin through mechanisms yet to be elucidated. It has been speculated that beta-lactam inactivation of select E. faecium penicillin binding proteins (PBPs) may play a pivotal role in this sensitization process. To characterize the specific PBP inacti...

CyanoLyase (http://cyanolyase.genouest.org/) is a manually curated sequence and motif database of phycobilin lyases and related proteins. These enzymes catalyze the covalent ligation of chromophores (phycobilins) to specific binding sites of phycobiliproteins (PBPs). The latter constitute the building bricks of phycobilisomes, the major light-harvesting systems of cyanobacteria and red algae. P...

Penicillin-binding proteins (PBPs) are enzymes involved in the synthesis of peptidoglycan structures in Bacillus subtilis such as the vegetative cell wall and the spore cortex. The B. subtilis sequencing project has identified a gene (orf16, EMBL accession number D38161) which exhibits significant sequence similarity to genes encoding class B high-molecular-weight PBPs. We have found that orf16...

Periplasmic binding proteins (PBPs) are a large family of molecular transporters that play a key role in nutrient uptake and chemotaxis in Gram-negative bacteria. All PBPs have characteristic two-domain architecture with a central interdomain ligand-binding cleft. Upon binding to their respective ligands, PBPs undergo a large conformational change that effectively closes the binding cleft. This...