Bacterial, Viral and Parasitic Pathogens and Colorectal Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Infectious Agents and Cancer".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 9098

Special Issue Editor

Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA
Interests: cancer epidemiology; infection and cancer; gastrointestinal cancer

Special Issue Information

Dear Colleagues,

Infection has been estimated to account for 15% of cancer incidence worldwide. There have been several viral, bacterial, and parasitic pathogens that have been causally linked to human cancers, including Helicobacter pylori, Hepatitis virus types B and C, human papillomavirus (HPV), Epstein–Barr virus, Kaposi’s sarcoma-associated herpes virus Human T-cell lymphotropic virus Opisthorchis viverrini, and Clonorchis sinensis and Schistosoma haematobium. Nevertheless, to date, no specific microbial pathogens have been conclusively linked to human colorectal cancer, despite the fact that gut contains trillions of microorganisms. Nonetheless, potential involvements of various pathogens, including Pylori non-Pylori Helicobacters, HPV, Polyomavirus, TT virus, Fusobacterium, Bacteroides, Prevotella, and Schistosoma japonicum and Blastocystis has been long suggested. Other studies have highlighted roles of bacterial specific metabolic activities to produce hydrogen sulfide, butyrate, and secondary bile acids. Given a growing number of publications in this field, a timely update and synthesis of current knowledge is warranted.

This Special Issue of Cancers is therefore intended to encompass original research articles and comprehensive reviews on epidemiological research, animal models, and clinical studies on the association between known, understudied or novel pathogens and colorectal cancer or their precursor lesions, such as polys or inflammatory bowel disease, studies to address interaction between microbial pathogens and traditional colorectal cancer risk factors, intervention/experimental studies with probiotics or fecal transplant, studies to identify and characterize virulent factors of known pathogens in colorectal carcinogenesis and methodological issues in study design, specimen collection/processing, and bioinformatic analysis.

Dr. Ikuko Kato
Guest Editor

Manuscript Submission Information

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Keywords

  • colorectal cancer
  • bacteria
  • viruses
  • parasites

Published Papers (5 papers)

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Editorial

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3 pages, 191 KiB  
Editorial
Bacterial, Viral and Parasitic Pathogens and Colorectal Cancer
by Ikuko Kato
Cancers 2023, 15(13), 3353; https://doi.org/10.3390/cancers15133353 - 26 Jun 2023
Cited by 1 | Viewed by 836
Abstract
Several viral, bacterial, and parasitic pathogens have been designated as human carcinogens by the World Health Organization [...] Full article
(This article belongs to the Special Issue Bacterial, Viral and Parasitic Pathogens and Colorectal Cancer)

Research

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19 pages, 4310 KiB  
Article
Therapeutic Target Identification and Inhibitor Screening against Riboflavin Synthase of Colorectal Cancer Associated Fusobacterium nucleatum
by Norah A. Alturki, Mutaib M. Mashraqi, Khurshid Jalal, Kanwal Khan, Zarrin Basharat and Ahmad Alzamami
Cancers 2022, 14(24), 6260; https://doi.org/10.3390/cancers14246260 - 19 Dec 2022
Cited by 6 | Viewed by 1982
Abstract
Colorectal cancer (CRC) ranks third among all cancers in terms of prevalence. There is growing evidence that gut microbiota has a role in the development of colorectal cancer. Fusobacterium nucleatum is overrepresented in the gastrointestinal tract and tumor microenvironment of patients with CRC. [...] Read more.
Colorectal cancer (CRC) ranks third among all cancers in terms of prevalence. There is growing evidence that gut microbiota has a role in the development of colorectal cancer. Fusobacterium nucleatum is overrepresented in the gastrointestinal tract and tumor microenvironment of patients with CRC. This suggests the role of F. nucleatum as a potential risk factor in the development of CRC. Hence, we aimed to explore whole genomes of F. nucleatum strains related to CRC to predict potential therapeutic markers through a pan-genome integrated subtractive genomics approach. In the current study, we identified 538 proteins as essential for F. nucleatum survival, 209 non-homologous to a human host, and 12 as drug targets. Eventually, riboflavin synthase (RiS) was selected as a therapeutic target for further processing. Three different inhibitor libraries of lead-like natural products, i.e., cyanobactins (n = 237), streptomycins (n = 607), and marine bacterial secondary metabolites (n = 1226) were screened against it. After the structure-based study, three compounds, i.e., CMNPD3609 (−7.63) > Malyngamide V (−7.03) > ZINC06804365 (−7.01) were prioritized as potential inhibitors of F. nucleatum. Additionally, the stability and flexibility of these compounds bound to RiS were determined via a molecular dynamics simulation of 50 ns. Results revealed the stability of these compounds within the binding pocket, after 5 ns. ADMET profiling showed compounds as drug-like, non-permeable to the blood brain barrier, non-toxic, and HIA permeable. Pan-genomics mediated drug target identification and the virtual screening of inhibitors is the preliminary step towards inhibition of this pathogenic oncobacterium and we suggest mouse model experiments to validate our findings. Full article
(This article belongs to the Special Issue Bacterial, Viral and Parasitic Pathogens and Colorectal Cancer)
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12 pages, 1296 KiB  
Article
Tumour Colonisation of Parvimonas micra Is Associated with Decreased Survival in Colorectal Cancer Patients
by Thyra Löwenmark, Anna Löfgren-Burström, Carl Zingmark, Ingrid Ljuslinder, Michael Dahlberg, Sofia Edin and Richard Palmqvist
Cancers 2022, 14(23), 5937; https://doi.org/10.3390/cancers14235937 - 30 Nov 2022
Cited by 10 | Viewed by 1275
Abstract
Increasing evidence suggests that the gut microbiota may impact colorectal cancer (CRC) development and progression. In this study, the tumour colonisation of two CRC-associated bacteria, Parvimonas micra and Fusobacterium nucleatum, was studied in relation to patient survival in a cohort of 257 [...] Read more.
Increasing evidence suggests that the gut microbiota may impact colorectal cancer (CRC) development and progression. In this study, the tumour colonisation of two CRC-associated bacteria, Parvimonas micra and Fusobacterium nucleatum, was studied in relation to patient survival in a cohort of 257 CRC patients. Colonisation of P. micra and F. nucleatum was analysed in fresh frozen tumour tissue (n = 112) and in faeces (n = 250) by qPCR. When analysing tumour tissues, both P. micra and F. nucleatum were found to be associated with decreased five-year cancer-specific survival, an association that remained significant in multivariable analysis for P. micra. Furthermore, we found significant associations of high levels of P. micra and F. nucleatum with tumour molecular characteristics, i.e., tumours mutated in BRAFV600E, and tumours of the MSI subtype. The analysis of faecal samples showed weaker associations with prognosis and tumour molecular characteristics. In conclusion, our findings support a novel association of tumour colonisation of P. micra with decreased patient survival. A better understanding of the role of the gut microbiota in CRC might contribute to the advancement of prognostic tools and new targets for therapy. Full article
(This article belongs to the Special Issue Bacterial, Viral and Parasitic Pathogens and Colorectal Cancer)
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10 pages, 685 KiB  
Article
Latent Microsporidia Infection Prevalence as a Risk Factor in Colon Cancer Patients
by Fernando Redondo, Carolina Hurtado-Marcos, Fernando Izquierdo, Carmen Cuéllar, Soledad Fenoy, Yanira Sáez, Ángela Magnet, Lorena Galindo-Regal, Natalia Uribe, Manuel López-Bañeres, Ana Isabel Jiménez, Antonio Llombart-Cussac, Carmen Del Águila and Juan Carlos Andreu-Ballester
Cancers 2022, 14(21), 5342; https://doi.org/10.3390/cancers14215342 - 29 Oct 2022
Cited by 3 | Viewed by 1591
Abstract
Microsporidia are opportunistic intracellular parasites, generating serious pathology in individuals with a compromised immune system. Infection by microsporidia inhibits p53 and Caspase 3, proteins involved in apoptosis and the cell cycle, which are vital in the malignant process of epithelial cells. The presence [...] Read more.
Microsporidia are opportunistic intracellular parasites, generating serious pathology in individuals with a compromised immune system. Infection by microsporidia inhibits p53 and Caspase 3, proteins involved in apoptosis and the cell cycle, which are vital in the malignant process of epithelial cells. The presence of microsporidia in the intestinal tissues of 87 colon cancer (CC) patients and 25 healthy controls was analyzed by real-time PCR and an immunofluorescence antibody test. Anti-Encephalitozoon antibodies were analyzed in serum samples by ELISA (enzyme linked immunosorbent assay). In 36 (41.3%) CC cases, microsporidia infections were identified in their tissues vs. no cases among control subjects (p < 0.0001). An increase in IgG and IgE anti-Encephalitozoon antibodies was found in patients with CC, which would demonstrate continuous and previous contact with the parasite. The high prevalence of microsporidia in tissues and the seroprevalence in patients with CC suggest a relationship between microsporidia and the etiopathogenesis of CC. Full article
(This article belongs to the Special Issue Bacterial, Viral and Parasitic Pathogens and Colorectal Cancer)
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Review

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15 pages, 3661 KiB  
Review
Genotoxins: The Mechanistic Links between Escherichia coli and Colorectal Cancer
by Ya Wang and Kai Fu
Cancers 2023, 15(4), 1152; https://doi.org/10.3390/cancers15041152 - 10 Feb 2023
Cited by 6 | Viewed by 2766
Abstract
Emerging evidence indicates bacterial infections contribute to the formation of cancers. Bacterial genotoxins are effectors that cause DNA damage by introducing single- and double-strand DNA breaks in the host cells. The first bacterial genotoxin cytolethal distending toxin (CDT) was a protein identified in [...] Read more.
Emerging evidence indicates bacterial infections contribute to the formation of cancers. Bacterial genotoxins are effectors that cause DNA damage by introducing single- and double-strand DNA breaks in the host cells. The first bacterial genotoxin cytolethal distending toxin (CDT) was a protein identified in 1987 in a pathogenic strain in Escherichia coli (E. coli) isolated from a young patient. The peptide-polyketide genotoxin colibactin is produced by the phylogenetic group B2 of E. coli. Recently, a protein produced by attaching/effacing (A/E) pathogens, including enteropathogenic and enterohemorrhagic E. coli (EPEC and EHEC) and their murine equivalent Citrobacter rodentium (CR), has been reported as a novel protein genotoxin, being injected via the type III secretion system (T3SS) into host cells and harboring direct DNA digestion activity with a catalytic histidine-aspartic acid dyad. These E. coli-produced genotoxins impair host DNA, which results in senescence or apoptosis of the target cells if the damage is beyond repair. Conversely, host cells can survive and proliferate if the genotoxin-induced DNA damage is not severe enough to kill them. The surviving cells may accumulate genomic instability and acquire malignant traits. This review presents the cellular responses of infection with the genotoxins-producing E. coli and discusses the current knowledge of the tumorigenic potential of these toxins. Full article
(This article belongs to the Special Issue Bacterial, Viral and Parasitic Pathogens and Colorectal Cancer)
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