PR002820 (Project)

Description:The project aims to discover antibiotics and characterize their mechanisms of action. We investigate proteobacteria that live symbiotically with animals as the source of the antibiotics. Specifically, bacteria live in the gills of shipworm mollusks, providing the cellulases needed for the mollusks to consume wood in the sea. The bacteria also contain large numbers of biosynthetic pathways for potential antibiotics, at least some of which are secreted into the animals where they likely act to impact the symbiosis. Because the antibiotics are made and secreted on animals, they are less likely to have direct impacts on animal cells. Among early hit compounds discovered, turnercyclamycins are lipodedpsipeptides that kill many multidrug-resistant, Gram-negative pathogens with clinical relevance. One of the goals of our project is to understand how turnercyclamycins work to kill bacteria that are resistant to other lipopeptide antibiotics, such as colistin. Here, we have studied this by comparing the impacts of colistin and turneryclamycin on bacterial membranes and the phospholipidome. By performing these and related studies on antibiotics produced by symbiotic bacteria, their mechanisms of action are unveiled.