Bacteria require phase separation for fitness in the mammalian gut

Science. 2023 Mar 17;379(6637):1149-1156. doi: 10.1126/science.abn7229. Epub 2023 Mar 16.

Abstract

Therapeutic manipulation of the gut microbiota holds great potential for human health. The mechanisms bacteria use to colonize the gut therefore present valuable targets for clinical intervention. We now report that bacteria use phase separation to enhance fitness in the mammalian gut. We establish that the intrinsically disordered region (IDR) of the broadly and highly conserved transcription termination factor Rho is necessary and sufficient for phase separation in vivo and in vitro in the human commensal Bacteroides thetaiotaomicron. Phase separation increases transcription termination by Rho in an IDR-dependent manner. Moreover, the IDR is critical for gene regulation in the gut. Our findings expose phase separation as vital for host-commensal bacteria interactions and relevant for novel clinical applications.

MeSH terms

  • Animals
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / physiology
  • Bacteroides thetaiotaomicron* / genetics
  • Bacteroides thetaiotaomicron* / physiology
  • Female
  • Gastrointestinal Microbiome* / genetics
  • Gastrointestinal Microbiome* / physiology
  • Genetic Fitness*
  • Germ-Free Life
  • Humans
  • Intrinsically Disordered Proteins* / chemistry
  • Intrinsically Disordered Proteins* / genetics
  • Intrinsically Disordered Proteins* / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein Domains
  • RNA Helicases* / chemistry
  • RNA Helicases* / genetics
  • RNA Helicases* / physiology
  • Rho Factor* / chemistry
  • Rho Factor* / genetics
  • Rho Factor* / physiology
  • Transcription Termination, Genetic

Substances

  • Intrinsically Disordered Proteins
  • Bacterial Proteins
  • RNA Helicases
  • Rho Factor