Figure 7. Bacteroides fitness is conditional on Acyl-CoA transferase expression and butyrate in vivo.

(A) Schematic demonstrating Bacteroides fitness based on interactions of BT_3193/BVU_1163 gene function, expression, and presence of a specific metabolite butyrate. Fitness represented in green (high) and red (low).

(B) Correlation between relative DNA abundance and relative expression of the Acyl-CoA transferase BT_3193/BVU_1163 of fecal samples from 26 human subjects in low versus high levels of fecal butyrate or high succinate (Benjamini-Hochberg false discovery rate (FDR) approach with a conservative FDR q-value < 0.05). See also Figure S6A.

(C) (left) Schematic of butyrate acting as a sugar- and strain-specific fitness switch in the Bacteroides. For three representative sugars, for which each Bacteroides species/strains (indicated by shades of blue) utilize and grow (high fitness indicated in green), butyrate results in differential impact on fitness at the species and strain level. (right) Model of the genetic and molecular mechanisms mediating variation in the inhibitory effect of butyrate among the Bacteroides. Butyrate enters the cell and is converted to butyryl-CoA through the activity of an Acyl-CoA transferase. An Acyl-CoA thioesterase then hydrolyzes butyryl-CoA decreasing cellular accumulation of this candidate toxic product. In the sensitive Bv, BVU_1163 (Acyl-CoA transferase) is highly expressed (4 enzyme symbols) leading to greater production of butyryl-CoA, and the poorly conserved Acyl-CoA thioesterase homolog in Bv (BVU_0767) results in butyryl-CoA accumulation.