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Published on: July 28, 2010
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.
Introduction:
Gut microbiota is a key player in colorectal cancer (CRC) proliferation. Parvimonas micra (P. micra), an obligate anaerobic bacterium that colonizes the oral cavity and gastrointestinal tract, has been implicated in CRC development. However, its virulence factors and pathogenic mechanisms remain poorly understood.
Objectives:
We aimed to explore the strain-level differences of P. micra in promoting the development of CRC, and the role of the virulence factor SirTM in pathogenic mechanisms.
Methods:
Utilizing an optimized culturomics approach, we isolated 99 strains of P. micra from the mucosal surfaces of CRC tissues. Through APCmin/+ mouse model experiments and whole genome sequencing of the strains, the role of virulence factors in promoting CRC development was explored. Protein mass spectrometry, transcriptome sequencing, and CUT&Tag combined analysis were used to investigate the pathogenic mechanism of virulence factors in P. micra.
Results:
We isolated 99 strains of P. micra from the mucosal surfaces of CRC tissues post-surgery, revealing strain-level variations in CRC promotion through whole genomics analysis and experiments. We identified SirTM of P. micra, a potential virulence factor possessing ADP-ribosyltransferase activity, which was experimentally validated to drive CRC progression. Further investigation determined that SirTM targets histone H2B, and their interaction facilitates CRC development via the CEBPβ/SAA1/IL-17C signaling pathway. Moreover, SirTM was evaluated as a potential biomarker target, and SAA1 as a potential therapeutic target in clinical CRC samples.
Conclusion:
P. micra can enter CRC cells to release SirTM and modify H2B with ADP-ribosylation, thereby promoting the development of CRC through the CEBPβ/SAA1/IL-17C pathway.
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.
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