Structural basis of iron piracy by a prominent human gut symbiont

Abstract

AbstractIron is an essential element that can be growth-limiting in microbial communities, particularly those present within host organisms. To acquire iron, many bacteria secrete siderophores, secondary metabolites that chelate ferric iron. These iron chelates can be transported back into the cell via TonB-dependent transporters in the outer membrane, followed by intracellular liberation of the iron.Salmonellaproduces siderophores during gut infection. In response to iron starvation, the human gut symbiontBacteroides thetaiotaomicronupregulates an iron piracy system, XusABC, which steals iron-bound siderophores from the invadingSalmonella. Here, we investigated the molecular details of ferric enterobactin uptake by the XusAB complex. Our crystal and cryogenic electron microscopy structures explain how the XusB lipoprotein recognises iron-bound siderophores and passes them on to the XusA TonB-dependent transporter for translocation across the outer membrane. Moreover, our results suggest that XusABC and homologous systems can transport a variety of siderophores with different iron-chelating functional groups.