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.
Adaptation to free-living drives loss of beneficial endosymbiosis through metabolic trade-offs
Symbioses are widespread (1) and underpin the function of diverse ecosystems (2-6), but their evolutionary stability is challenging to explain (7,8). Fitness trade-offs between con-trasting



