The genetic landscape of antibiotic sensitivity in Staphylococcus aureus.

Despite the critical importance of essential genes, systems-level investigations of their contribution to antibiotic sensitivity have been limited. Using CRISPR Adaptation-mediated Library Manufacturing (CALM), we generated ultra-dense CRISPR interference (CRISPRi) libraries in methicillin-sensitive and -resistant strains of Staphylococcus aureus, which allowed us to quantify gene fitness on a global scale across ten clinically relevant antibiotics. This led to the identification of a comprehensive set of known and novel biological processes modulating bacterial fitness in the antibiotics.