Mode of Interaction of Two S. aureus Enzymes with the Bacterial Cell Wall (2023)

Peptidoglycan (PG) is a giga-dalton polymer constituting scaffold and integrity of bacterial cell wall (CW). PG is metabolised by a large and diverse group of PG hydrolases, guards of bacterial cell growth and division. PG hydrolases have been the focus of many studies over the years, but molecular understanding of their action within PG mesh is missing.
Our recent work fills this gap by providing structural knowledge on the interaction of two evolutionary related peptidases of the M23 family, lysostaphin and LytM, with short PG fragments and the entire sacculus. Through nuclear magnetic resonance, information-driven modelling, mass spectrometry, site-directed mutagenesis and biochemical approaches, we provide residue-resolution details of their interaction with the bacterial cell wall. This allows us to address long-standing question regarding the relationship between selectivity and specificity of lysostaphin and LytM and their physiological function. We propose a new model in which PG cross-linking affects the activity of these two enzymes differently .
With this work, we intend to provide better understanding of the action and regulation of PG hydrolyses in the complex mesh of the bacterial cell wall. In broader perspective, our work will serve to underpin future research concerning the development of new antimicrobial agents.

Collaboration : I. Sabala ( Warsaw, Poland)