Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b

LS Gonzalez-Delgado, H Walters-Morgan, B Salamaga, AJ Robertson, AM Hounslow, E Jagielska, I Sabała, MP Williamson, AL Lovering, S Mesnage

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
282 Downloads (Pure)

Abstract

Lysostaphin is a bacteriolytic enzyme targeting peptidoglycan, the essential component of the bacterial cell envelope. It displays a very potent and specific activity toward staphylococci, including methicillin-resistant Staphylococcus aureus. Lysostaphin causes rapid cell lysis and disrupts biofilms, and is therefore a therapeutic agent of choice to eradicate staphylococcal infections. The C-terminal SH3b domain of lysostaphin recognizes peptidoglycans containing a pentaglycine crossbridge and has been proposed to drive the preferential digestion of staphylococcal cell walls. Here we elucidate the molecular mechanism underpinning recognition of staphylococcal peptidoglycan by the lysostaphin SH3b domain. We show that the pentaglycine crossbridge and the peptide stem are recognized by two independent binding sites located on opposite sides of the SH3b domain, thereby inducing a clustering of SH3b domains. We propose that this unusual binding mechanism allows synergistic and structurally dynamic recognition of S. aureus peptidoglycan and underpins the potent bacteriolytic activity of this enzyme.
Original languageEnglish
Pages (from-to)24-30
Number of pages7
JournalNature Chemical Biology
Volume16
Issue number1
DOIs
Publication statusPublished - 4 Nov 2019

Fingerprint

Dive into the research topics of 'Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b'. Together they form a unique fingerprint.

Cite this