» Articles » PMID: 36693067

Fn-Dps, a Novel Virulence Factor of Fusobacterium Nucleatum, Disrupts Erythrocytes and Promotes Metastasis in Colorectal Cancer

Overview
Journal PLoS Pathog
Specialty Microbiology
Date 2023 Jan 24
PMID 36693067
Authors
Affiliations
Soon will be listed here.
Abstract

Fusobacterium nucleatum (Fn) is a critical colorectal cancer (CRC)-associated bacterium. DNA hunger/stationary phase protective proteins (Dps) are bacterial ferritins that protect DNA from oxidative stress. However, little is known about the regulatory roles of Fn-Dps towards host cellular functions. Here, we identified Fn-Dps from the culture supernatant of Fn by mass spectrometry, and prepared the recombinant of Fn-Dps protein. We show a novel virulence protein of Fn, Fn-Dps, which lyses and disrupts erythrocytes by the competition for iron acquisition. Also, Fn-Dps facilitates intracellular survival of Fn in macrophages by upregulating the expression of the chemokine CCL2/CCL7. In addition, Fn-Dps can elicit a strong humoral immune response, and mucosal immunization with Fn-Dps conferred protection against Fn in the intestinal tract. Moreover, a high level of anti-Fn-Dps antibody was prevalent in populations, and elevated anti-Fn-Dps antibody levels were observed in CRC patients. Furthermore, Fn-Dps promotes the migration of CRC cells via the CCL2/CCL7-induced epithelial-mesenchymal transition (EMT) and promotes CRC metastasis in vivo.

Citing Articles

Current Evidence on the Relation Between Microbiota and Oral Cancer-The Role of -A Narrative Review.

Chiscuzzu F, Crescio C, Varrucciu S, Rizzo D, Sali M, Delogu G Cancers (Basel). 2025; 17(2).

PMID: 39857953 PMC: 11763498. DOI: 10.3390/cancers17020171.


Virulence factor discovery identifies associations between the Fic gene family and Fap2 fusobacteria in colorectal cancer microbiomes.

Nakatsu G, Ko D, Michaud M, Franzosa E, Morgan X, Huttenhower C mBio. 2025; 16(2):e0373224.

PMID: 39807864 PMC: 11796403. DOI: 10.1128/mbio.03732-24.


Multi-omics analysis reveals the interplay between intratumoral bacteria and glioma.

Li T, Zhao Z, Peng M, Zhang L, Wang C, Luo F mSystems. 2024; 10(1):e0045724.

PMID: 39660865 PMC: 11748541. DOI: 10.1128/msystems.00457-24.


Reexamining the role of subspecies in clinical and experimental studies.

Krieger M, Guo M, Merritt J Gut Microbes. 2024; 16(1):2415490.

PMID: 39394990 PMC: 11486156. DOI: 10.1080/19490976.2024.2415490.


Leucine restriction ameliorates Fusobacterium nucleatum-driven malignant progression and radioresistance in nasopharyngeal carcinoma.

Guo S, Xing S, Wu Z, Chen F, Pan X, Li Q Cell Rep Med. 2024; 5(10):101753.

PMID: 39357525 PMC: 11513822. DOI: 10.1016/j.xcrm.2024.101753.


References
1.
Su S, Wu W, He C, Liu Q, Song E . Breaking the vicious cycle between breast cancer cells and tumor-associated macrophages. Oncoimmunology. 2015; 3(8):e953418. PMC: 4292267. DOI: 10.4161/21624011.2014.953418. View

2.
Yamamura K, Izumi D, Kandimalla R, Sonohara F, Baba Y, Yoshida N . Intratumoral Levels Predict Therapeutic Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma. Clin Cancer Res. 2019; 25(20):6170-6179. PMC: 6801075. DOI: 10.1158/1078-0432.CCR-19-0318. View

3.
Ueshima J, Shoji M, Ratnayake D, Abe K, Yoshida S, Yamamoto K . Purification, gene cloning, gene expression, and mutants of Dps from the obligate anaerobe Porphyromonas gingivalis. Infect Immun. 2003; 71(3):1170-8. PMC: 148816. DOI: 10.1128/IAI.71.3.1170-1178.2003. View

4.
Kurzejamska E, Sacharczuk M, Landazuri N, Kovtonyuk O, Lazarczyk M, Ananthaseshan S . Effect of Chemokine (C-C Motif) Ligand 7 (CCL7) and Its Receptor (CCR2) Expression on Colorectal Cancer Behaviors. Int J Mol Sci. 2019; 20(3). PMC: 6387027. DOI: 10.3390/ijms20030686. View

5.
Chen Y, Chen Y, Zhang J, Cao P, Su W, Deng Y . Promotes Metastasis in Colorectal Cancer by Activating Autophagy Signaling via the Upregulation of CARD3 Expression. Theranostics. 2020; 10(1):323-339. PMC: 6929621. DOI: 10.7150/thno.38870. View