publishedVersion
Deciphering the evolution of metallo-β-lactamases: A journey from the test tube to the bacterial periplasm
Autor
López, Carolina
Delmonti, Juliana
Bonomo, Robert A.
Vila, Alejandro J.
Institución
Resumen
Understanding the evolution of metallo-β-lactamases (MBLs) is fundamental to deciphering the mechanistic basis of resistance to carbapenems in pathogenic and opportunistic bacteria. Presently, these MBL-producing pathogens are linked to high rates of morbidity and mortality worldwide. However, the study of the biochemical and biophysical features of MBLs in vitro provides an incomplete picture of their evolutionary potential, since this limited and artificial environment disregards the physiological context where evolution and selection take place. Herein, we describe recent efforts aimed to address the evolutionary traits acquired by different clinical variants of MBLs in conditions mimicking their native environment (the bacterial periplasm) and considering whether they are soluble or membrane-bound proteins. This includes addressing the metal content of MBLs within the cell under zinc starvation conditions and the context provided by different bacterial hosts that result in particular resistance phenotypes. Our analysis highlights recent progress bridging the gap between in vitro and in-cell studies. Fil: López, Carolina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Metaloproteínas (IBR-CONICET); Argentina. Fil: Delmonti, Juliana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Metaloproteínas (IBR-CONICET); Argentina. Fil: Bonomo, Robert A. Veterans Affairs Northeast Ohio Healthcare System. Research Service; United States. Fil: Bonomo, Robert A. Case Western Reserve University School of Medicine. Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics; United States. Fil: Bonomo, Robert A. Veterans Affairs Northeast Ohio Healthcare System. Medical Service and GRECC; United States. Fil: Bonomo, Robert A. CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology. U.S. Department of Veterans Affairs; United States. Fil: Vila, Alejandro J. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Metaloproteínas (IBR-CONICET); Argentina. Fil: Vila, Alejandro J. CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology. U.S. Department of Veterans Affairs; United States. Fil: Vila, Alejandro J. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Biofísica; Argentina.