Effect of the adhesive antibiotic TA on adhesion and initial growth of E-coli on silicone rubber

Catheter-associated urinary tract infection is the most common nosocomial infection, and contributes to patient morbidity and mortality. We investigated the effect that the TA adhesive antibiotic had on adhesion and initial growth in urine of Escherichia coli on silicone rubber. The TA antibiotic had reduced adhesion, and inhibited initial growth of the bacteria on the surface. Since adhesion and initial growth on the surface are an essential part of biofilm formation and subsequent infection, we speculate that the TA antibiotic coating might decrease the infection rate associated with indwelling urinary catheter. (C) 2000 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved

Structures of lipoprotein signal peptidase II from Staphylococcus aureus complexed with antibiotics globomycin and myxovirescin.

Antimicrobial resistance is a major global threat that calls for new antibiotics. Globomycin and myxovirescin are two natural antibiotics that target the lipoprotein-processing enzyme, LspA, thereby compromising the integrity of the bacterial cell envelope. As part of a project aimed at understanding their mechanism of action and for drug development, we provide high-resolution crystal structures of the enzyme from the human pathogen methicillin-resistant Staphylococcus aureus (MRSA) complexed with globomycin and with myxovirescin. Our results reveal an instance of convergent evolution. The two antibiotics possess different molecular structures. Yet, they appear to inhibit identically as non-cleavable tetrahedral intermediate analogs. Remarkably, the two antibiotics superpose along nineteen contiguous atoms that interact similarly with LspA. This 19-atom motif recapitulates a part of the substrate lipoprotein in its proposed binding mode. Incorporating this motif into a scaffold with suitable pharmacokinetic properties should enable the development of effective antibiotics with built-in resistance hardiness