BtuB TonB-dependent transporters and BtuG surface lipoproteins form stable complexes for vitamin B 12 uptake in gut Bacteroides

Vitamin B 12 (cobalamin) is required for most human gut microbes, many of which are dependent on scavenging to obtain this vitamin. Since bacterial densities in the gut are extremely high, competition for this keystone micronutrient is severe. Contrasting with Enterobacteria, members of the dominant genus Bacteroides often encode several BtuB vitamin B 12 outer membrane transporters together with a conserved array of surface-exposed B 12 -binding lipoproteins. Here we show that the BtuB transporters from Bacteroides thetaiotaomicron form stable, pedal bin-like complexes with surface-exposed BtuG lipoprotein lids, which bind B 12 with high affinities. Closing of the BtuG lid following B 12 capture causes destabilisation of the bound B 12 by a conserved BtuB extracellular loop, causing translocation of the vitamin to BtuB and subsequent transport. We propose that TonB-dependent, lipoprotein-assisted small molecule uptake is a general feature of Bacteroides spp. that is important for the success of this genus in colonising the human gut.