Lipidated β-lactamases: From bench to bedside

BAHR, GUILLERMO; BAHR, GUILLERMO; GONZÁLEZ, LISANDRO J.; GONZÁLEZ, LISANDRO J.; VILA, ALEJANDRO J.; VILA, ALEJANDRO J.

FUTURE MICROBIOLOGY

FUTURE MEDICINE LTD

Lugar: Londres; Año: 2016 vol. 11 p. 1495 - 1498

1746-0913

Carbapenemases represent one of the largestclinical threats to the action of carbapenems, last resort drugs for thetreatment of healthcare-associated infections caused by Gram-negative bacteria. Metallo-β-lactamases (MBLs) areZn(II)-dependent enzymes that constitute the largest family of carbapenemasesof clinical impact. Among them, the New-DelhiMetallo-β-lactamase (NDM-1) is a plasmid-encoded carbapenemase that hasexperienced the fastest and widest geographical spread, having been detected inmore than 80 countries worldwide since its identification in 2008.Remarkably, the clinical success of this resistance determinant does not seemto be associated with the dissemination of a particular clone or geneticstructure. We have recentlysuggested that this particular success is due to the cellular localization ofNDM-1: while all other known MBLs are soluble periplasmic proteins, NDM-1 is alipoprotein anchored to the inner leaflet of the outer membrane inGram-negative bacteria.Despite NDM-1 was reported as a lipidated protein in 2011, this fact was regarded as abiochemical curiosity and deserved little attention until recently, when wereported that lipidation and membrane anchoring confer unique evolutionaryadvantages to NDM-1.