Staphylococcus aureus sacculus mediates activities of M23 hydrolases

Bacterial wall maintenance, and in particular the peptidoglycan that forms the basis of bacterial cell wall scaffolding, is one of the main targets of antibiotics, and understanding its fine regulation is crucial to effectively combating resistance phenomena.

Researchers from the NMR group at IBS, in collaboration with a group of Polish microbiologists, studied the high lytic activity of the enzymes Lysostaphin and LytM against the bacterium S. aureus, by targeting the glycil-glycine bridge linking the peptide strands of the bacterial wall polymer. Monitoring of the catalytic reaction revealed these two enzymes acted in a similar way on the polymer fragments but only Lysostaphin was capable of solubilising the entire polymer. Analysis of the nuclear magnetic resonance (NMR) characterization data led to coherent models for the docking of the enzymes on the polymer. The researchers have shown that each enzyme reacts distinctly with the polymer depending on the complexity of cross-linking and therefore has different biological functions (cf. figure). Using nuclear magnetic resonance (NMR) combined with mass spectrometry, this work proposes a model in which peptidoglycan cross-linking affects the activity and selectivity of the enzymes Lysostaphin and LytM
differently, underpinning the specific role of each structurally related enzyme. These results highlight the complex
interaction between enzymes and their substrates. They pave the way for targeted antibacterial strategies.

Staphylococcus aureus sacculus mediates activities of M23 hydrolases. Razew A, Laguri C, Vallet A, Bougault C, Kaus-Drobek M, Sabala I, Simorre JP. Nature Communications 2023 ; 14(1):6706.

Contact : Jean-Pierre Simorre (IBS/Biomolecular NMR Spectroscopy Group)