Enhanced pathogenicity of Fusobacterium nucleatum adapted to oxidative stress

Silva, Vânia L.; Diniz, Cláudio Galuppo; Cara, Denise Carmona; Santos, Simone Gonçalves dos; Nicoli, Jacques R.; Carvalho, Maria Auxiliadora Roque de; Farias, Luiz M.

doi:10.1016/j.micpath.2005.07.002

Cited by 21 publications

(26 citation statements)

References 35 publications

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“…Interestingly, F . nucleatum can adapt to oxidative stress [35,36] and exhibits enhanced pathogenicity in mice under these conditions [37,38], implying potential dual roles in CRC pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Bacterially-Associated Transcriptional Remodelling in a Distinct Genomic Subtype of Colorectal Cancer Provides a Plausible Molecular Basis for Disease Development

2016

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The relevance of specific microbial colonisation to colorectal cancer (CRC) disease pathogenesis is increasingly recognised, but our understanding of possible underlying molecular mechanisms that may link colonisation to disease in vivo remains limited. Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC. We show that colonisation by E. faecalis and high levels of Fusobacterium is associated with a specific transcriptomic subtype of CRC that is characterised by CpG island methylation, microsatellite instability and a significant increase in inflammatory and DNA damage pathways. Analysis of the significant, bacterially-associated changes in host gene expression, both at the level of individual genes as well as pathways, revealed a transcriptional remodeling that provides a plausible mechanistic link between specific bacterial colonisation and colorectal cancer disease development and progression in this subtype; these included upregulation of REG3A, REG1A and REG1P in the case of high-level colonization by Fusobacterium, and CXCL10 and BMI1 in the case of colonisation by E. faecalis. The enrichment of both E. faecalis and Fusobacterium in this CRC subtype suggests that polymicrobial colonisation of the colonic epithelium may well be an important aspect of colonic tumourigenesis.

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Section: Discussionmentioning

confidence: 99%

Bacterially-Associated Transcriptional Remodelling in a Distinct Genomic Subtype of Colorectal Cancer Provides a Plausible Molecular Basis for Disease Development

2016

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“…F. nucleatum is a moderate anaerobe that tolerates low oxygen concentrations (16). Evidence exists that it possesses capacity for further oxygen adaptation (17,18) and even that oxidative stress can increase Fusobacterium pathogenicity (19). All three species have repeatedly been reported from suppurative infections, including pulmonary empyema, liver abscesses, and brain abscesses (5,(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Massive Parallel Sequencing Provides New Perspectives on Bacterial Brain Abscesses

et al. 2014

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m Rapid development within the field of massive parallel sequencing (MPS) is about to bring this technology within reach for diagnostic microbiology laboratories. We wanted to explore its potential for improving diagnosis and understanding of polymicrobial infections, using bacterial brain abscesses as an example. We conducted a prospective nationwide study on bacterial brain abscesses. Fifty-two surgical samples were included over a 2-year period. The samples were categorized as either spontaneous intracerebral, spontaneous subdural, or postoperative. Bacterial 16S rRNA genes were amplified directly from the specimens and sequenced using Ion Torrent technology, with an average of 500,000 reads per sample. The results were compared to those from culture-and Sanger sequencing-based diagnostics. Compared to culture, MPS allowed for triple the number of bacterial identifications. Aggregatibacter aphrophilus, Fusobacterium nucleatum, and Streptococcus intermedius or combinations of them were found in all spontaneous polymicrobial abscesses. F. nucleatum was systematically detected in samples with anaerobic flora. The increased detection rate for Actinomyces spp. and facultative Gram-negative rods further revealed several species associations. We suggest that A. aphrophilus, F. nucleatum, and S. intermedius are key pathogens for the establishment of spontaneous polymicrobial brain abscesses. In addition, F. nucleatum seems to be important for the development of anaerobic flora. MPS can accurately describe polymicrobial specimens when a sufficient number of reads is used to compensate for unequal species concentrations and principles are defined to discard contaminant bacterial DNA in the subsequent data analysis. This will contribute to our understanding of how different types of polymicrobial infections develop. O ur understanding of polymicrobial infections has been hindered by our limited possibilities for describing them. Recent investigations of bacterial brain abscesses using universal amplification of the bacterial 16S rRNA gene, followed by Sanger sequencing of cloned amplicons, have revealed that only a fraction of the bacteria present are identified by culture (1, 2). Nevertheless, this approach has limitations when it comes to detecting smaller subpopulations in a multispecies community, unless very high numbers of clones are sequenced (3). This is problematic, since the species structure of an abscess may change over time and pathogens important for establishing the infection potentially remain at only low concentrations in the more mature abscesses. Furthermore, the species that are important for maintaining and expanding the abscess might primarily exist close to the abscess wall and do not necessarily dominate in the pus obtained by aspiration. Rapid development within the field of massive parallel sequencing technologies (MPS) is about to provide the diagnostic laboratories with tools that can characterize even the most complex microbial communities. The aim of the present study was to use recent adva...

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“…17 Viable bacterial cells can be recovered from infected host cells, including colonic cell lines, after 24 h or more 36 (and unpublished observations), which is remarkable considering that the bacteria are obligate anaerobes; it is likely that the bacteria upregulate genes involved in aero tolerance in response to certain cues taken from the infective process. 37 Bacterial survival within host cells may be dependent on the cell line and/or F. nucleatum strain studied as some studies 38 were unable to recover viable F. nucleatum from cultured IL1β. We observed significant correlations between infection with highly invasive isolates and concomitant upregulation of MUC2 and TNFα gene expression, as well as variable ability among these invasive isolates to upregulate MUC1 gene expression.…”

Section: F Nucleatum Invasion and Subsequent Fatementioning

confidence: 99%

Fusobacterium nucleatum

2011

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The Gram-negative, non-sporulating, obligately anaerobic species, Fusobacterium nucleatum, is rapidly gaining notoriety as a pathogen with a surprising number of associated diseases. Recently, we have found that F. nucleatum is a more common resident of the GI tract than originally thought, and thus, through several studies, we have attempted to determine its gut-relevant potential for virulence. We have found that F. nucleatum possesses a number of pathogenic traits with relevance to gut diseases such as inflammatory bowel disease (IBD), however, we have also documented strain-associated differences in virulence. An intriguing picture emerges that paints F. nucleatum as both conferring beneficial as well as detrimental effects on host cells; and we suggest that the ultimate effects of F. nucleatum infection in the gut are a consequence of the microbes with which this species aggregates.

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Enhanced pathogenicity of Fusobacterium nucleatum adapted to oxidative stress

Cited by 21 publications

References 35 publications

Bacterially-Associated Transcriptional Remodelling in a Distinct Genomic Subtype of Colorectal Cancer Provides a Plausible Molecular Basis for Disease Development

Bacterially-Associated Transcriptional Remodelling in a Distinct Genomic Subtype of Colorectal Cancer Provides a Plausible Molecular Basis for Disease Development

Massive Parallel Sequencing Provides New Perspectives on Bacterial Brain Abscesses

Fusobacterium nucleatum

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