Deciphering the evolution of metallo-β-lactamases: a journey from the test tube to the bacterial periplasm

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Año: 2022

0021-9258

Understanding the evolution of metallo-β-lactamases (MBLs) is fundamental todeciphering the mechanistic basis of resistance to carbapenems in pathogenic andopportunistic bacteria. Presently, these MBL producing pathogens are linked to high rates ofmorbidity and mortality worldwide. However, the study of the biochemical and biophysicalfeatures of MBLs in vitro provides an incomplete picture of their evolutionary potential, sincethis limited and artificial environment disregards the physiological context where evolution andselection take place. Herein, we describe recent efforts aimed to address the evolutionary traitsacquired by different clinical variants of MBLs in conditions mimicking their native environment(the bacterial periplasm) and considering whether they are soluble or membrane-boundproteins. This includes addressing the metal content of MBLs within the cell under zincstarvation conditions, and the context provided by different bacterial hosts that result inparticular resistance phenotypes. Our analysis highlights recent progress bridging the gapbetween in vitro and in-cell studies