PEPLYS

Bacterial surface proteins play a critical role in fundamental processes such as cell growth, division, and environmental interactions. In pathogens, these proteins are essential for tissue invasion and evading the host immune system. Core to all these functions is the ability to bind to the bacterial cell wall, and thus be appropriately displayed for interaction with the environment. This project will focus on a protein domain called LysM (for Lysin Motif) found in all bacterial species. LysM mediates non-covalent attachment of proteins to peptidoglycan (PG), the essential component of the bacterial cell envelope which is the target of the most important antibiotic ever discovered, penicillin LysM domains are found in bacteria, plants, animals, and viruses, are absent in Archaea. These domains typically consist of one to twelve motifs, each about 45 amino acids long, with a conserved ßaaß fold. Enzymes linked to LysM are used by bacteria to remodel the cell wall, build and destroy septa, and in pathogenesis. While the LysM fold is conserved, the amino acid sequences vary, and how these variations affect binding affinity or specificity is unknown. It has been shown that LysM motifs fold independently, allowing for additive binding strength without cooperative folding. In this project we will focus on two key enzymes in Enterococcus faecalis, AtlA and AtlB, that contain LysM domains and contribute to PG remodeling during growth. AtlA is mainly responsible for septum cleavage during cell division, while AtlB aids in overall PG turnover. The major challenge lies in understanding the diversity of LysM domains. This research aims to explore how cell wall composition and LysM domain properties influence this targeting. Given the threat posed by E. faecalis as a drug-resistant pathogen, the findings could provide groundbreaking insights into bacterial cell wall interactions and lead to innovative strategies for combating antibiotic-resistant infections