Structural basis of broad-spectrum β-lactam resistance in Staphylococcus aureus.

ABSTRACT: Broad-spectrum β-lactam antibiotic resistance in Staphylococcus aureus is a global healthcare burden^1,2. In clinical strains, resistance is largely controlled by BlaR1³, a receptor that senses β-lactams through the acylation of its sensor domain, inducing transmembrane signalling and activation of the cytoplasmic-facing metalloprotease domain⁴. The metalloprotease domain has a role in BlaI derepression, inducing blaZ (β-lactamase PC1) and mecA (β-lactam-resistant cell-wall transpeptidase PBP2a) expression^3-7. Here, overcoming hurdles in isolation, we show that BlaR1 cleaves BlaI directly, as necessary for inactivation, with no requirement for additional components as suggested previously⁸. Cryo-electron microscopy structures of BlaR1-t

SUBMITTER: Alexander JAN 

PROVIDER: S-EPMC9834060 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature