An ancient respiratory enzyme metabolically modulates Fusobacterium nucleatum virulence.

Although viewed as an oral commensal, the Gram-negative is an opportunistic pathogen that can traverse to extra-oral sites, such as placenta and colon, promoting adverse pregnancy outcomes and colorectal cancer, respectively. How this anaerobe sustains the various metabolically changing environments enabling its virulence potential remains unclear. Here, we demonstrate that the Rnf complex is key to metabolism and virulence as genetic disruption of Rnf causes pleiotropic defects in polymicrobial interaction, biofilm formation, cell growth and morphology, hydrogen sulfide production, and ATP synthesis. Targeted metabolomic profiling demonstrates that the loss of this highly conserved respiratory enzyme significantly diminishes catabolism of numerous amino acids, which negatively impacts fusobacterial virulence as tested in a preterm birth model in mice.