RNA landscape of the emerging cancer-associated microbe Fusobacterium nucleatum

Nat Microbiol. 2021 Aug;6(8):1007-1020. doi: 10.1038/s41564-021-00927-7. Epub 2021 Jul 8.

Abstract

Fusobacterium nucleatum, long known as a constituent of the oral microflora, has recently garnered renewed attention for its association with several different human cancers. The growing interest in this emerging cancer-associated bacterium contrasts with a paucity of knowledge about its basic gene expression features and physiological responses. As fusobacteria lack all established small RNA-associated proteins, post-transcriptional networks in these bacteria are also unknown. In the present study, using differential RNA-sequencing, we generate high-resolution global RNA maps for five clinically relevant fusobacterial strains-F. nucleatum subspecies nucleatum, animalis, polymorphum and vincentii, as well as F. periodonticum-for early, mid-exponential growth and early stationary phase. These data are made available in an online browser, and we use these to uncover fundamental aspects of fusobacterial gene expression architecture and a suite of non-coding RNAs. Developing a vector for functional analysis of fusobacterial genes, we discover a conserved fusobacterial oxygen-induced small RNA, FoxI, which serves as a post-transcriptional repressor of the major outer membrane porin FomA. Our findings provide a crucial step towards delineating the regulatory networks enabling F. nucleatum adaptation to different environments, which may elucidate how these bacteria colonize different compartments of the human body.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Fusobacterium Infections / microbiology*
  • Fusobacterium nucleatum / classification
  • Fusobacterium nucleatum / genetics*
  • Fusobacterium nucleatum / growth & development
  • Fusobacterium nucleatum / physiology
  • Humans
  • Neoplasms / microbiology*
  • Porins / genetics
  • Porins / metabolism
  • RNA, Bacterial / genetics*
  • RNA, Bacterial / metabolism

Substances

  • Bacterial Proteins
  • Porins
  • RNA, Bacterial