Fusobacterium nucleatum — symbiont, opportunist and oncobacterium

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Abstract

Fusobacterium nucleatum has long been found to cause opportunistic infections and has recently been implicated in colorectal cancer; however, it is a common member of the oral microbiota and can have a symbiotic relationship with its hosts. To address this dissonance, we explore the diversity and niches of fusobacteria and reconsider historic fusobacterial taxonomy in the context of current technology. We also undertake a critical reappraisal of fusobacteria with a focus on F. nucleatum as a mutualist, infectious agent and oncogenic microorganism. In this Review, we delve into recent insights and future directions for fusobacterial research, including the current genetic toolkit, our evolving understanding of its mechanistic role in promoting colorectal cancer and the challenges of developing diagnostics and therapeutics for F. nucleatum.

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Fig. 1: The organizing role of Fusobacterium nucleatum in oral biofilms.
Fig. 2: Oral and extraoral diseases associated with Fusobacterium nucleatum.
Fig. 3: Mechanisms by which Fusobacterium nucleatum may contribute to colorectal carcinogenesis.

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Acknowledgements

This work is supported by US National Institutes of Health (NIH) grant R01CA154426. C.A.B. is the Dennis and Marsha Dammerman fellow of the Damon Runyon Cancer Research Foundation (DRG-2205-14).

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Both authors researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and edited the manuscript before submission.

Correspondence to Wendy S. Garrett.

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Competing interests

W.S.G. serves on the Scientific Advisory Boards of Evelo Biosciences, Kintai Therapeutics and uBiome. W.S.G. is a consultant for BioMx and has been a consultant for Janssen, Pfizer and Merck. W.S.G. is a senior editor at eLife, which publishes the ‘Reproducibility Project: Cancer Biology’ experimental designs and methods as registered reports and results as replication studies.

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Supplementary Information

Glossary

Combinatorial labelling and spectral imaging–fluorescence in situ hybridization

(CLASI-FISH). This technique enables detection of ten to several hundred distinct microbial taxa by using combinations of fluorophores coupled to different oligonucleotide probes that target unique regions of the 16S ribosomal RNA (rRNA) gene.

Osteomyelitis

Infectious or non-infectious inflammation of the bone.

Pericarditis

Infectious or non-infectious inflammation of the sac-like tissue that surrounds the heart.

Chorioamnionitis

Infectious or non-infectious inflammation of the chorion and amnion (the fetal membranes) and the amniotic fluid, which can occur before or during labour.

Lemierre syndrome

Infectious thrombophlebitis of the internal jugular vein, which is often caused by F. necrophorum. It can occur in the setting of a fusobacterial throat infection with peritonsillar abscess formation, but in the modern antibiotic era it remains fairly rare. The syndrome is named after Andrew Lemierre, who published a case report in the 1930s that identified throat infections as the cause of several anaerobic sepsis cases.

CpG island methylator phenotype

(CIMP). A state of epigenetic instability in which promoter CpG island sites become hypermethylated, which results in turning off of genes, including tumour suppressor genes.

Microsatellite instability

A condition in which impaired DNA mismatch repair leads to genetic hypermutation. Colorectal tumours can be described as microsatellite instable-high (MSI-high) or microsatellite stable (MSS).

Familial adenomatous polyposis

A genetic disorder that is caused by mutation of the APC gene and results in numerous tumours of the large bowel. Classically, these colon tumours form during the teenage years and the number of tumours increases with age, but there are also attenuated variants.

Colorectal adenomas

Non-malignant tumours occurring in the colon and rectum that can develop into cancer.

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Brennan, C.A., Garrett, W.S. Fusobacterium nucleatum — symbiont, opportunist and oncobacterium. Nat Rev Microbiol 17, 156–166 (2019) doi:10.1038/s41579-018-0129-6

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