Tamiflu: the battle for secret drug data

Summary Efficient nutrient acquisition in the competitive human gut is essential for microbial persistence. While polysaccharides have been well-studied nutrients for the gut microbiome, other resources such as co-factors and nucleic acids have been less examined. We describe a series of ribose utilization systems (RUSs) that are broadly represented in Bacteroidetes and appear to have diversified to allow access to ribose from a variety of substrates. One Bacteroides thetaiotaomicron RUS variant is critical for competitive gut colonization in a diet-specific fashion. Using molecular genetics, we probed the nature of the ribose source underlying this diet-specific phenotype, revealing that hydrolytic functions in RUS (e.g., to cleave ribonucleosides) are present but dispensable. Instead, ribokinases that are activated in vivo and participate in cellular ribose-phosphate metabolism are essential. Our results underscore the extensive mechanisms that gut symbionts have evolved to access nutrients and how metabolic context determines the impact of these functions in vivo.