Project
role of linear azol(in)e-containing peptides in the lifestyle of foodborne human pathogens
Linear azol(in)e-containing peptides (LAPs) are a group of bacterial ribosomally synthesized and posttranslationally modified peptides, often exhibiting strong antimicrobial activity. Despite their structural similarity, the mode of action and activity spectrum of LAPS show a remarkable diversity of which the structural basis and functional significance is poorly understood. While LAPS displays a cytolytic activity towards host cells and contributes to virulence of some pathogens, like the cytolysin streptolysin S (SLS) in streptococci, other, often structurally related SLS-Iike LAPS are not cytolytic and display antibacterial activity. This project proposal aims to investigate the function, structure-activity relationship, ecological role, and evolutionary flexibility of LAPs from Listeria monocytogenes, Staphylococcus aureus and Bacillus cereus, three notorious foodborne pathogens with different lifestyles, and in which biosynthetic gene clusters for SLS-Iike LAPS have been identified. The approach will be based on a combination of microbiology, bioinformatics, laboratory adaptive evolution, and bacterial genetics.