Fatal Case of Liver and Brain Abscesses Due to Fusobacterium nucleatum

Toumeh, Nadia; Mudireddy, Megha; Smith, Brian N.; Guerrero, Dubert M.

doi:10.7759/cureus.19671

Cited by 3 publications

(2 citation statements)

References 8 publications

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“…Fusobacterium nucleatum is a gram-negative obligately anaerobic bacillus that is normally found in the oropharyngeal and upper respiratory tracts. Fusobacterium nucleatum is an important pathogen in abscesses [5] .…”

Section: Introductionmentioning

confidence: 99%

Metagenomic next-generation sequencing identified a brain abscess caused by mixed oral anaerobe infection: A case report

Ma,

Liu,

Liu

et al. 2024

Infectious Medicine

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Section: Introductionmentioning

confidence: 99%

Metagenomic next-generation sequencing identified a brain abscess caused by mixed oral anaerobe infection: A case report

Ma,

Liu,

Liu

et al. 2024

Infectious Medicine

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“…Fusobacterium, especially the species Fusobacterium nucleatum (Fn), has garnered significant attention since this bacterium was reported to be overrepresented in colorectal cancer tumors more than a decade ago [23][24][25] . Classical studies mainly focused on the role of Fn in oral infections and diseases including periodontitis 26,27 , severe organ infections [28][29][30][31] , and preterm birth [32][33][34] . The majority of recent studies have shifted to focus on a potential direct causal role in adverse cancer phenotypes including heightened inflammation [35][36][37] , production of a carcinogenic metabolite 38 , induced metastasis [39][40][41] , DNA damage [42][43][44] , increased resistance to frontline chemotherapy drugs 45,46 , and overall worse patient prognosis 35,47,48 .…”

Section: Introductionmentioning

confidence: 99%

DNA methyltransferase enhanced Fusobacterium nucleatum genetics

Umaña

Nguyen

Sanders

et al. 2022

Preprint

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Bacterial restriction-modification (R-M) systems are a first line immune defense against foreign DNA from viruses and other bacteria. While R-M systems are critical in maintaining genome integrity, R-M nucleases unfortunately present significant barriers to targeted genetic modification. Bacteria of the genus Fusobacterium are oral, Gram-negative, anaerobic, opportunistic pathogens that are implicated in the progression and severity of multiple cancers and tissue infections, yet our understanding of their direct roles in disease have been severely hindered by their genetic recalcitrance. Here, we demonstrate a path to overcome these barriers in Fusobacterium by using native DNA methylation as a host mimicry strategy to bypass R-M system cleavage of user introduced plasmid DNA. We report the identification, characterization, and successful use of Fusobacterium nucleatum (Fn) Type II and III DNA methyltransferase (DMTase) enzymes to produce a multi-fold increase in gene knockout efficiency in the strain Fusobacterium nucleatum subsp. nucleatum 23726 (Fnn 23726), as well as the first efficient gene knockouts and complementations in Fnn 25586. We show plasmid protection can be accomplished in vitro with purified enzymes, as well as in vivo in an E. coli host that constitutively expresses Fnn DMTase enzymes. By characterizing specific DMTases that are critical for bypassing R-M systems, we have enhanced our understanding of potential enzyme combinations, with the goal of expanding these studies to genetically modify clinical isolates of Fusobacterium that have thus far been inaccessible to molecular characterization. This proof-of-concept study provides a roadmap to guide molecular microbiology efforts of the scientific community to facilitate the discovery of new Fusobacterium virulence genes, thereby leading to a new era of characterizing how an oral opportunistic pathogen contributes to an array of human infections and diseases.IMPORTANCEFusobacterium nucleatum is an oral opportunistic pathogen associated with diseases including cancer and preterm birth. Our understanding of how this bacterium modulates human disease has been hindered by a lack of genetic systems. Here we show that F. nucleatum DNA methyltransferase modified plasmid DNA overcomes the transformation barrier and allows the development of genetic systems in previously inaccessible strains. We present a strategy that can be expanded to enable the genetic modification of clinical isolates, thereby fostering investigational studies to uncover novel host-pathogen interactions in Fusobacterium.

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