Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b

Lysostaphin is a bacteriolytic enzyme targeting peptidoglycan, the essential component of the bacterial cell envelope. It displays a very potent and specific activity toward staphylococci, including methicillin-resistant Staphylococcus aureus. Lysostaphin causes rapid cell lysis and disrupts biofilms, and is therefore a therapeutic agent of choice to eradicate staphylococcal infections. The C-terminal SH3b domain of lysostaphin recognizes peptidoglycans containing a pentaglycine crossbridge and has been proposed to drive the preferential digestion of staphylococcal cell walls. Here we elucidate the molecular mechanism underpinning recognition of staphylococcal peptidoglycan by the lysostaphin SH3b domain. We show that the pentaglycine crossbridge and the peptide stem are recognized by two independent binding sites located on opposite sides of the SH3b domain, thereby inducing a clustering of SH3b domains. We propose that this unusual binding mechanism allows synergistic and structurally dynamic recognition of S. aureus peptidoglycan and underpins the potent bacteriolytic activity of this enzyme

A state of the art review on optimal practices to prevent, recognize, and manage complications associated with intravascular devices in the critically ill.

Intravascular catheters are inserted into almost all critically ill patients. This review provides up-to-date insight into available knowledge on epidemiology and diagnosis of complications of central vein and arterial catheters in ICU. It discusses the optimal therapy of catheter-related infections and thrombosis. Prevention of complications is a multidisciplinary task that combines both improvement of the process of care and introduction of new technologies. We emphasize the main component of the prevention strategies that should be used in critical care and propose areas of future investigation in this field