Functional redundancy and plasticity in staphylococcus aureus vitamin B1 metabolism ensure stable colonisation in the environment and in the host

Abstract

In this study, we explored fastidious metabolic pathways of Staphylococcus aureus and showed that the organism is auxotrophic for thiamine. Thiamine plays a key role in carbohydrate metabolism and is essential for ATP synthesis in both prokaryotes and eukaryotes. We demonstrated that thiamine deprivation is lethal in S. aureus and explored the essential pathway involved in vitamin biosynthesis and transport. Moreover, we have shown that thiVWX is a thiamine, TMP, and TPP transporter instead of a previously hypothesized HMP (thiamine precursor) transporter. Lastly, we also showed how the S. aureus thiamine pathway redundancy is necessary for S. aureus survival in different environmental niches. With multi-drug resistant (MDR) pathogen becoming a global issue and the lack of new drug discovery, our results open up new revenue for developing drugs against the MDR pathogen.