Victoria Gebler

The Prevotellaceae family comprises abundant, taxonomically diverse bacteria of the human microbiota that exhibit remarkable intraspecies variability and distinct phenotypes during host-microbe interactions. Yet functional investigations are hampered by the limited genetic tractability of this medically important bacterial family, rendering it understudied. Here, we apply antisense oligomer (ASO) technology to selectively inhibit translation of single or multiple mRNAs across nine Prevotellaceae species. Using ftsZ - and mreB -related phenotypes as morphogenic readouts, we demonstrate that ASOs can function as a tunable system to study essential gene function. Further, we show that ASOs can selectively deplete target species from a synthetic Bacteroidales community. These results establish ASOs as practical tools for functional genomics and community modulation in otherwise genetically intractable anaerobic microbiota members.

Herein, we present a synthetic procedure for the facile and general preparation of novel S-alkenyl and dienyl phosphoro(di)thioates for the first time. Extensive mechanistic investigations support that the reactions rely on a photochemical excitation of a halogen-bonding complex, formed with a phosphorothioate salt and an alkenyl or dienyl bromide, which light-induced fragmentation leads to the formation of the desired products through a radical-based pathway. The substrate scope is broad and exhibits a wide functional group tolerance in the formation of the final compounds, including molecules derived from natural products, all with unknown and potentially interesting biological properties. Eventually, a very efficient continuous flow protocol was developed for the upscale of these reactions.