Control of transcription termination factor Rho by phase separation in Bacteroides thetaiotaomicron

Liquid-liquid phase separation (LLPS) alters the activity of proteins by segregating them into membraneless compartments. In the gut commensal bacterium Bacteroides thetaiotaomicron, transcription termination factor Rho (BtRho) undergoes LLPS during carbon starvation and in the mammalian gut, which increases its termination activity, alters gene expression, and promotes bacterial fitness. Specific short sequences within the intrinsically disordered region (IDR) of BtRho are highly conserved in Bacteroides Rho sequelogs and responsible for RNA-mediated BtRho LLPS, intradomain interactions that promote or restrict BtRho LLPS, and control of BtRho LLPS during carbon starvation. Our findings establish a fundamental role for phase separation in host-microbe interactions and reveal how a nutritional stress governs LLPS of an essential transcription factor.