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Anaerobe Apr 2023We set out to identify and characterize prophages within genomes of published Fusobacterium strains, and to develop qPCR-based methods to characterize intra- and...
OBJECTIVES
We set out to identify and characterize prophages within genomes of published Fusobacterium strains, and to develop qPCR-based methods to characterize intra- and extra-cellular induction of prophage replication in a variety of environmental contexts.
METHODS
Various in silico tools were used to predict prophage presence across 105 Fusobacterium spp. Genomes. Using the example of the model pathogen, Fusobacterium nucleatum subsp. animalis strain 7-1, qPCR was used with DNase I treatment to determine induction of its 3 predicted prophages ɸFunu1, ɸFunu2, and ɸFunu3, across several conditions.
RESULTS
116 predicted prophage sequences were found and analyzed. An emerging association between the phylogenetic history of a Fusobacterium prophage and that of its host was detected, as was the presence of genes encoding putative host fitness factors (e.g. ADP-ribosyltransferases) in distinct subclusters of prophage genomes. For strain 7-1, a pattern of expression for ɸFunu1, ɸFunu2, and ɸFunu3 was established indicating that ɸFunu1 and ɸFunu2 are capable of spontaneous induction. I Salt and mitomycin C exposure were able to promote induction of ɸFunu2. A range of other biologically relevant stressors, including exposure to pH, mucin and human cytokines showed no or minimal induction of these same prophages. ɸFunu3 induction was not detected under tested conditions.
CONCLUSION
The heterogeneity of Fusobacterium strains is matched by their prophages. While the role of Fusobacterium prophages in host pathogenicity remains unclear, this work provides the first overview of clustered prophage distribution among this enigmatic genus and describes an effective assay for quantifying mixed samples of prophages that cannot be detected by plaque assay.
Topics: Humans; Prophages; Phylogeny; Fusobacterium
PubMed: 36801248
DOI: 10.1016/j.anaerobe.2023.102718 -
Nature Reviews. Microbiology Oct 2022
Topics: Biofilms; Fusobacterium; Fusobacterium nucleatum
PubMed: 35915254
DOI: 10.1038/s41579-022-00787-w -
British Journal of Hospital Medicine... Jan 2022
Topics: Abdomen; Anti-Bacterial Agents; Fusobacterium necrophorum; Humans; Lemierre Syndrome
PubMed: 35129386
DOI: 10.12968/hmed.2021.0301 -
Microbiology Spectrum Aug 2023Fusobacterium nucleatum is a Gram-negative bacterium that has been identified as an important pathogenic gut bacterium associated with colorectal cancer. Compared with...
Fusobacterium nucleatum is a Gram-negative bacterium that has been identified as an important pathogenic gut bacterium associated with colorectal cancer. Compared with the normal intestine, the pH value of the tumor microenvironment is weakly acidic. The metabolic changes of F. nucleatum in the tumor microenvironment, especially the protein composition of its outer membrane vesicles, remain unclear. Here, we systematically analyzed the effect of environmental pH on the proteome of outer membrane vesicles (OMVs) from F. nucleatum by tandem mass tag (TMT) labeling-high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A total of 991 proteins were identified in acidic OMVs (aOMVs) and neutral OMVs (nOMVs), including known virulence proteins and putative virulence proteins. Finally, 306 upregulated proteins and 360 downregulated proteins were detected in aOMVs, and approximately 70% of the expression of OMV proteins was altered under acidic conditions. A total of 29 autotransporters were identified in F. nucleatum OMVs, and 13 autotransporters were upregulated in aOMVs. Interestingly, three upregulated autotransporters (D5REI9, D5RD69, and D5RBW2) show homology to the known virulence factor Fap2, suggesting that they may be involved in various pathogenic pathways such as the pathway for binding with colorectal cancer cells. Moreover, we found that more than 70% of MORN2 domain-containing proteins may have toxic effects on host cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that a number of proteins were significantly enriched in multiple pathways involving fatty acid synthesis and butyrate synthesis. Seven metabolic enzymes involved in fatty acid metabolism pathways were identified in the proteomic data, of which 5 were upregulated and 2 were downregulated in aOMVs, while 14 metabolic enzymes involved in the butyric acid metabolic pathway were downregulated in aOMVs. In conclusion, we found a key difference in virulence proteins and pathways in the outer membrane vesicles of F. nucleatum between the tumor microenvironment pH and normal intestinal pH, which provides new clues for the prevention and treatment of colorectal cancer. F. nucleatum is an opportunistic pathogenic bacterium that can be enriched in colorectal cancer tissues, affecting multiple stages of colorectal cancer development. OMVs have been demonstrated to play key roles in pathogenesis by delivering toxins and other virulence factors to host cells. By employing quantitative proteomic analysis, we found that the pH conditions could affect the protein expression of the outer membrane vesicles of F. nucleatum. Under acidic conditions, approximately 70% of the expression of proteins in OMVs was altered. Several virulence factors, such as type 5a secreted autotransporter (T5aSSs) and membrane occupation and recognition nexus (MORN) domain-containing proteins, were upregulated under acidic conditions. A large number of proteins showed significant enrichments in multiple pathways involving fatty acid synthesis and butyrate synthesis. Proteomics analysis of the outer membrane vesicles secreted by pathogenic bacteria in the acidic tumor microenvironment is of great significance for elucidating the pathogenicity mechanism and its application in vaccine and drug delivery vehicles.
Topics: Humans; Fusobacterium nucleatum; Proteomics; Type V Secretion Systems; Chromatography, Liquid; Tandem Mass Spectrometry; Virulence Factors; Membrane Proteins; Colorectal Neoplasms; Fatty Acids; Bacterial Outer Membrane Proteins; Tumor Microenvironment
PubMed: 37341631
DOI: 10.1128/spectrum.00394-23 -
Expert Reviews in Molecular Medicine Apr 2023Breast cancer was the most commonly diagnosed cancer worldwide in 2020. Greater understanding of the factors which promote tumour progression, metastatic development and... (Review)
Review
Breast cancer was the most commonly diagnosed cancer worldwide in 2020. Greater understanding of the factors which promote tumour progression, metastatic development and therapeutic resistance is needed. In recent years, a distinct microbiome has been detected in the breast, a site previously thought to be sterile. Here, we review the clinical and molecular relevance of the oral anaerobic bacterium in breast cancer. is enriched in breast tumour tissue compared with matched healthy tissue and has been shown to promote mammary tumour growth and metastatic progression in mouse models. Current literature suggests that modulates immune escape and inflammation within the tissue microenvironment, two well-defined hallmarks of cancer. Furthermore, the microbiome, and specifically, has been shown to affect patient response to therapy including immune checkpoint inhibitors. These findings highlight areas of future research needed to better understand the influence of in the development and treatment of breast cancer.
Topics: Animals; Mice; Fusobacterium nucleatum; Colorectal Neoplasms; Base Composition; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Tumor Microenvironment
PubMed: 37009688
DOI: 10.1017/erm.2023.9 -
Cancer Research Communications Nov 2022() is a gram-negative oral anaerobe and prevalent in colorectal cancer. encodes a unique amyloid-like adhesin, FadA complex (FadAc), consisting of intact pre-FadA and...
UNLABELLED
() is a gram-negative oral anaerobe and prevalent in colorectal cancer. encodes a unique amyloid-like adhesin, FadA complex (FadAc), consisting of intact pre-FadA and cleaved mature FadA, to promote colorectal cancer tumorigenesis. We aimed to evaluate circulating anti-FadAc antibody levels as a biomarker for colorectal cancer. Circulating anti-FadAc IgA and IgG levels were measured by ELISA in two study populations. In study 1, plasma samples from patients with colorectal cancer ( = 25) and matched healthy controls ( = 25) were obtained from University Hospitals Cleveland Medical Center. Plasma levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (mean ± SD: 1.48 ± 1.07 μg/mL) compared with matched healthy controls (0.71 ± 0.36 μg/mL; = 0.001). The increase was significant in both early (stages I and II) and advanced (stages III and IV) colorectal cancer. In study 2, sera from patients with colorectal cancer ( = 50) and patients with advanced colorectal adenomas ( = 50) were obtained from the Weill Cornell Medical Center biobank. Anti-FadAc antibody titers were stratified according to the tumor stage and location. Similar as study 1, serum levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (2.06 ± 1.47 μg/mL) compared with patients with colorectal adenomas (1.49 ± 0.99 μg/mL; = 0.025). Significant increase was limited to proximal cancers, but not distal tumors. Anti-FadAc IgG was not increased in either study population, suggesting that likely translocates through the gastrointestinal tract and interact with colonic mucosa. Anti-FadAc IgA, but not IgG, is a potential biomarker for early detection of colorectal neoplasia, especially for proximal tumors.
SIGNIFICANCE
, an oral anaerobe highly prevalent in colorectal cancer, secretes the amyloid-like FadAc to promote colorectal cancer tumorigenesis. We report that circulating levels of anti-FadAc IgA, but not IgG, are increased in patients with both early and advanced colorectal cancer compared with the healthy controls, and especially in those with proximal colorectal cancer. Anti-FadAc IgA may be developed into a serological biomarker for early detection of colorectal cancer.
Topics: Humans; Fusobacterium nucleatum; Colorectal Neoplasms; Adhesins, Bacterial; Carcinogenesis; Cell Transformation, Neoplastic; Biomarkers; Adenoma
PubMed: 36970057
DOI: 10.1158/2767-9764.CRC-22-0248 -
Archives of Disease in Childhood.... Aug 2022A 2-year-old previously well child presented to the emergency department with temperatures and lethargy. He was pale and looked unwell. He received a fluid bolus and was...
A 2-year-old previously well child presented to the emergency department with temperatures and lethargy. He was pale and looked unwell. He received a fluid bolus and was commenced on intravenous ceftriaxone. Pus was discharging from his left ear with postauricular swelling and erythema. Given clinical concerns, urgent neuroimaging was arranged.
Topics: Abscess; Child; Child, Preschool; Fusobacterium necrophorum; Humans; Jugular Veins; Male; Mastoiditis; Rare Diseases
PubMed: 33172868
DOI: 10.1136/archdischild-2020-320122 -
Journal of Oral Microbiology 2022Recently, the possibility that oral microbiomes is associated with oral squamous cell carcinoma (OSCC) initiation and progression has attracted attention; however, this...
OBJECTIVE
Recently, the possibility that oral microbiomes is associated with oral squamous cell carcinoma (OSCC) initiation and progression has attracted attention; however, this association is still unclear. Here, we comprehensively analyze the microbiome profiles of saliva samples using next-generation sequencing followed by determining the association between oral microbiome profiles and OSCC.
MATERIALS AND METHODS
Microbiome profiles in saliva samples from patients with OSCC, oral leukoplakia (OLK), and postoperative OSCC (Post) were analyzed. Candidate OSCC-associated bacteria were identified by comparing the bacterial diversity and relative abundance of each group based on these microbiome profiles, and their applicability as OSCC detection tools were evaluated.
RESULTS
There were significant differences in genus abundances (, and ) among the groups from saliva samples. In the OSCC group, compared with the OLK and Post groups, abundances of the genus , phylum and phylum were markedly increased and that of the genus and phylum were decreased.
CONCLUSION
The results suggested a strong association of these bacteria with OSCC. Especially, phylum was significantly associated with early recurrence of OSCC. Thus, oral microbiome analysis may have a potential of novel OSCC detection and prognostic tool.
PubMed: 35958277
DOI: 10.1080/20002297.2022.2105574 -
Frontiers in Cellular and Infection... 2022is a common oral opportunistic bacterium that can cause different infections. In recent years, studies have shown that is enriched in lesions in periodontal diseases,... (Review)
Review
is a common oral opportunistic bacterium that can cause different infections. In recent years, studies have shown that is enriched in lesions in periodontal diseases, halitosis, dental pulp infection, oral cancer, and systemic diseases. Hence, it can promote the development and/or progression of these conditions. The current study aimed to assess research progress in the epidemiological evidence, possible pathogenic mechanisms, and treatment methods of in oral and systemic diseases. Novel viewpoints obtained in recent studies can provide knowledge about the role of in hosts and a basis for identifying new methods for the diagnosis and treatment of -related diseases.
Topics: Fusobacterium Infections; Fusobacterium nucleatum; Humans; Mouth Neoplasms; Periodontal Diseases
PubMed: 35186795
DOI: 10.3389/fcimb.2022.815318 -
British Journal of Cancer Apr 2023Experimental evidence suggests a role of intratumour Fusobacterium nucleatum in the aggressive behaviour of gastrointestinal cancer through downregulating anti-tumour...
BACKGROUND
Experimental evidence suggests a role of intratumour Fusobacterium nucleatum in the aggressive behaviour of gastrointestinal cancer through downregulating anti-tumour immunity. We investigated the relationship between intratumour F. nucleatum and immune response to oesophageal cancer.
METHODS
Utilising an unbiased database of 300 resected oesophageal cancers, we measured F. nucleatum DNA in tumour tissue using a quantitative polymerase chain reaction assay, and evaluated the relationship between the abundance of F. nucleatum and the densities of T cells (CD8 + , FOXP3 + and PDCD1 + ), as well as lymphocytic reaction patterns (follicle lymphocytic reaction, peritumoural lymphocytic reaction, stromal lymphocytic reaction and tumour-infiltrating lymphocytes) in oesophageal carcinoma tissue.
RESULTS
F. nucleatum was significantly and inversely associated only with the peritumoural lymphocytic reaction (P = 0.0002). Compared with the F. nucleatum-absent group, the F. nucleatum-high group showed a much lower level of the peritumoural lymphocytic reaction (univariable odds ratio, 0.33; 95% confidence interval, 0.16-0.65; P = 0.0004). A multivariable model yielded a similar finding (multivariable odds ratio, 0.34; 95% confidence interval 0.16-0.69; P = 0.002).
CONCLUSIONS
Intratumour F. nucleatum is associated with a diminished peritumoural lymphocytic reaction, providing a platform for further investigations on the potential interactive roles between intratumour F. nucleatum and host immunity.
Topics: Humans; Colorectal Neoplasms; Fusobacterium nucleatum; Lymphocytes; Esophageal Neoplasms; Immunity
PubMed: 36599917
DOI: 10.1038/s41416-022-02112-x