Lipidated beta-lactamases: from bench to bedside

GONZÁLEZ LJ; BAHR G; VILA AJ

FUTURE MICROBIOLOGY

FUTURE MEDICINE LTD

Lugar: Londres; Año: 2016

1746-0913

Carbapenemases represent one of the largest clinical threats to the action of carbapenems; the last resort drugs for the treatment of healthcare-associated infections caused by Gram-negative bacteria. Metallo-β-lactamases (MBLs) are Zn(II)-dependent enzymes that constitute the largest family of carbapenemases of clinical impact. Among them, the New Delhi Metallo-β-lactamase (NDM-1) is a plasmid-encoded carbapenemase that has experienced the fastest and widest geographical spread, having been detected in more than 80 countries worldwide since its identification in 2008. Remarkably, the clinical success of this resistance determinant does not seem to be associated with the dissemination of a particular clone or genetic structure. We have recently suggested that this particular success is due to the cellular localization of NDM-1: while all other known MBLs are soluble periplasmic proteins, NDM-1 is a lipoprotein anchored to the inner leaflet of the outer membrane in Gram-negative bacteria. Despite NDM-1 being reported as a lipidated protein in 2011, this fact was regarded as a biochemical curiosity and deserved little attention until recently when we reported that lipidation and membrane anchoring confer unique evolutionary advantages to NDM-1.