2. Academic Validation
  3. Parvimonas micra-derived SirTM: An ADP-ribosyltransferase as a novel driver in colorectal cancer progression

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

  • J Adv Res. 2026 Mar 17:S2090-1232(26)00256-0. doi: 10.1016/j.jare.2026.03.035.
Yuxiao Chang 1,  Chao Yang 2,  Fengyi Hou 3,  Yubing Zhu 4,  Ziran Huang 5,  Likun Wang 5,  Yuejiao Liu 5,  Huan Zhang 6,  Xiaoming Qin 7,  Zichuang Hao 7,  Dong Li 5,  Yafang Tan 5,  Yinlan Bai 8,  Lei Ding 4,  Hong Gao 4,  Fachao Zhi 9,  Fanglin Zhang 8,  Yujing Bi 5,  Ruifu Yang 10
Affiliations

Affiliations

  • 1 State 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.
  • 2 The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.
  • 3 State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China; Department of Gastroenterology, The Key Laboratory of Advanced Interdisciplinary Studies Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 4 Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
  • 5 State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
  • 6 State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China; School of Public Health, Hebei Medical University, Shijiazhuang, China.
  • 7 State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China; Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 8 Department of Microbiology and Pathogen Biology, Air Force Medical University, Xi'an, China.
  • 9 Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 10 State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China; School of Public Health, Hebei Medical University, Shijiazhuang, China. Electronic address: [email protected].
PMID: 41850426 DOI: 10.1016/j.jare.2026.03.035
Abstract

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.

Keywords

ADP-ribosyltransferase; CEBPβ/SAA1/IL-17C pathway; Colorectal cancer; Histone H2B; Parvimonas micra.

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