Parvimonas micra-derived SirTM: An ADP-ribosyltransferase as a novel driver in colorectal cancer progression

Yuxiao Chang1, Chao Yang2, Fengyi Hou3

  • 1State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China; Department of Microbiology and Pathogen Biology, Air Force Medical University, Xi'an, China.

Abstract

Insights

Parvimonas micra releases the virulence factor SirTM, which promotes colorectal cancer (CRC) development by modifying histone H2B. This finding identifies potential diagnostic and therapeutic targets for CRC.

Area of Science:

  • Microbiology
  • Oncology
  • Molecular Biology

Background:

  • Gut microbiota plays a crucial role in colorectal cancer (CRC) proliferation.
  • Parvimonas micra (P. micra) is implicated in CRC development, but its virulence factors and pathogenic mechanisms are not well understood.

Purpose of the Study:

  • To investigate strain-level differences in P. micra's role in CRC development.
  • To elucidate the pathogenic mechanisms of the P. micra virulence factor SirTM.

Main Methods:

  • Isolation of 99 P. micra strains from CRC tissues using culturomics.
  • Whole genome sequencing, APCmin/+ mouse model, mass spectrometry, transcriptome sequencing, and CUT&Tag analysis to explore virulence factors and mechanisms.

Main Results:

  • Identified P. micra SirTM as a virulence factor with ADP-ribosyltransferase activity that drives CRC progression.
  • Demonstrated SirTM targets histone H2B, promoting CRC via the CEBPβ/SAA1/IL-17C pathway.
  • Evaluated SirTM as a potential biomarker and SAA1 as a therapeutic target in CRC samples.

Conclusions:

  • P. micra enters CRC cells, releasing SirTM to ADP-ribosylate histone H2B.
  • This process promotes CRC development through the CEBPβ/SAA1/IL-17C signaling pathway.