BtuB TonB-dependent transporters and BtuG surface lipoproteins form stable complexes for vitamin B₁₂ uptake in gut Bacteroides.

Abstract

Vitamin B₁₂ (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 B₁₂ outer membrane transporters together with a conserved array of surface-exposed B₁₂-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 B₁₂ with high affinities. Closing of the BtuG lid following B₁₂ capture causes destabilisation of the bound B₁₂ 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.