Molecular trade between bacteria and eukaryotic host mediated by membranous nanotubes

Microbiota and intestinal epithelium restrict pathogen growth by rapid nutrient consumption. We investigated how pathogens circumvent this obstacle to colonize the host. Utilizing enteropathogenic E. coli (EPEC), we show that host-attached bacteria obtain nutrients from infected host cell in a process we termed host nutrient extraction (HNE). We identified an inner-membrane protein complex, henceforth termed CORE as necessary and sufficient for HNE. The CORE is a key component of the EPEC injectisome and is known also as the export apparatus of the type III secretion system. However, here we show that it supports the formation of an alternative structure, composed of membranous nanotubes, protruding from the EPEC surface to directly contact the host. Remarkably, CORE complexes of diverse ancestries, including the distant CORE of B. subtilis flagellum, rescued the HNE capacity of EPEC lacking its native injectisome CORE. Further analysis show that formation of intercellular nanotubes by B. subtilis, as well as other species is dependent on their flagellum CORE. Notably, thousands of species across the entire bacterial kingdom contain flagella or injectisome genes and thus have the potential to form the CORE-nanotube organelle. Our results demonstrate that the CORE derived nanotube might be a widespread organelle that facilitates intercellular molecular trade between bacteria and eukaryotic host as well as among different bacterial species.