Multiple TonB homologs are important for carbohydrate utilization by Bacteroides thetaiotaomicron .

The human gut microbiota is able to degrade otherwise undigestible polysaccharides, largely through the activity of Bacteroides . Uptake of polysaccharides into Bacteroides is controlled by TonB-dependent transporters (TBDTs), whose transport is energized by an inner membrane complex composed of the proteins TonB, ExbB, and ExbD. Bacteroides thetaiotaomicron ( B. theta ) encodes 11 TonB homologs that are predicted to be able to contact TBDTs to facilitate transport. However, it is not clear which TonBs are important for polysaccharide uptake. Using strains in which each of the 11 predicted tonB genes are deleted, we show that TonB4 (BT2059) is important but not essential for proper growth on starch. In the absence of TonB4, we observed an increase in the abundance of TonB6 (BT2762) in the membrane of B. theta , suggesting functional redundancy of these TonB proteins. The growth of the single deletion strains on pectic galactan, chondroitin sulfate, arabinan, and levan suggests a similar functional redundancy of the TonB proteins. A search for highly homologous proteins across other Bacteroides species and recent work in Bacteroides fragilis suggests that TonB4 is widely conserved and may play a common role in polysaccharide uptake. However, proteins similar to TonB6 are found only in B. theta and closely related species, suggesting that the functional redundancy of TonB4 and TonB6 may be limited across Bacteroides . This study extends our understanding of the protein network required for polysaccharide utilization in B. theta and highlights differences in TonB complexes across Bacteroides species.IMPORTANCEThe human gut microbiota, including Bacteroides , is required for the degradation of otherwise undigestible polysaccharides. The gut microbiota uses polysaccharides as an energy source, and fermentation products such as short-chain fatty acids are beneficial to the human host. This use of polysaccharides is dependent on the proper pairing of a TonB protein with polysaccharide-specific TonB-dependent transporters; however, the formation of these protein complexes is poorly understood. In this study, we examine the role of 11 predicted TonB homologs in polysaccharide uptake. We show that two proteins, TonB4 and TonB6, may be functionally redundant. This may allow for the development of drugs targeting Bacteroides species containing only a TonB4 homolog with limited impact on species encoding the redundant TonB6.