Thermosensitive PBP2a requires extracellular folding factors PrsA and HtrA1 for Staphylococcus aureus MRSA β-lactam resistance.

ABSTRACT: Staphylococcus aureus is a major human pathogen and represents a clinical challenge because of widespread antibiotic resistance. Methicillin resistant Staphylococcus aureus (MRSA) is particularly problematic and originates by the horizontal acquisition of mecA encoding PBP2a, an extracellular membrane anchored transpeptidase, which confers resistance to β-lactam antibiotics by allosteric gating of its active site channel. Herein, we show that dual disruption of PrsA, a lipoprotein chaperone displaying anti-aggregation activity, together with HtrA1, a membrane anchored chaperone/serine protease, resulted in severe and synergistic attenuation of PBP2a folding that restores sensitivity to β-lactams such as oxacillin. Purified PBP2a has a pronounced unfolding transition in

SUBMITTER: Roch M 

PROVIDER: S-EPMC6858329 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature