Bacterial cell wall interactome by AF3
Abstract
Bacteria are surrounded by a protective peptidoglycan cell wall. Hence, the enzymes responsible for making this wall are the main targets of our most successful antibiotics. However, emerging resistant bacteria are eroding the efficacy of our antibiotic arsenal. Identifying new genetic determinants of the bacterial cell wall as antibiotic targets is of the highest international priority but requires an integrative, multidisciplinary approach. What is our goal? Our goal in this Wallenberg Scholar project is to identify the molecular repertoire of peptidoglycan biogenesis and remodeling in the pathogen Vibrio cholerae, determine the mechanisms that maintain homeostasis and those that promote plasticity, and ultimately find new and more effective antimicrobial therapies. The Cava lab has recently pioneered unique systems-level analytical approaches of the bacterial cell wall with dedicated bioinformatic tools. In less than 5 min, they can generate comprehensive peptidoglycan chemical profiles. The unprecedented high throughput of this technology makes it possible for the very first time to profile the cell wall of bacterial mutant libraries. However, the resulting tome of data needs deciphering with integrative mathematical analyses that can predict functional networks for further mechanistic and physiological studies. To exploit such massive relational data, we need high-performance computing to identify the complex interactions among cell wall proteins by Alphafold to facilitate a functional network data analysis.
