IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Membrane-anchoring stabilizes and favors secretion of New Delhi Metallo-beta-lactamase
Autor/es:
GUILLERMO BAHR; ROBERT A. BONOMO; LISANDRO JAVIER GONZALEZ; ELIZABETH M. NOLAN; TOSHIKI G. NAKASHIGE; ALEJANDRO JOSÉ VILA
Revista:
NATURE CHEMICAL BIOLOGY
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Lugar: Londres; Año: 2016 vol. 12 p. 516 - 522
ISSN:
1552-4450
Resumen:
Carbapenems, "last resort" beta-lactam antibiotics, are inactivated by zinc-dependent metallo-beta-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, since these enzymes are readily degraded in their non-metallated form. However, the New Delhi Metallo-beta-lactamase (NDM-1) is able to persist under conditions of metal depletion. NDM-1 is a lipidated protein anchored to the outer membrane of Gram-negative bacteria. Membrane-anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the blaNDM gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies.