Cytolethal Distending Toxin Promotes Replicative Stress Leading to Genetic Instability Transmitted to Daughter Cells

Tremblay, William; Mompart, Florence; Lopez, Elisa Isabel Garcia; Quaranta, Muriel; Bergoglio, Valérie; Hashim, Saleha; Bonnet, Delphine; Alric, Laurent; Mas, Emmanuel; Trouche, Didier; Vignard, Julien; Ferrand, Audrey; Mirey, Gladys; Fernandez-Vidal, Anne

doi:10.3389/fcell.2021.656795

Cited by 15 publications

(7 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It can contribute to carcinogenesis by inducing genetic instability in replicating epithelial stem cells, which is then passed on daughter cells. Moreover, it induces senescence in CD4 + T cells, reducing the efficiency of the immune system’s anticancer response (He et al 2019 ; Mathiasen et al 2021 ; Tremblay et al 2021 ).…”

Section: Microbes Drive Hallmarks Of Cancermentioning

confidence: 99%

Microbiota as the unifying factor behind the hallmarks of cancer

Benešová

Křížová

Kverka

2023

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

The human microbiota is a complex ecosystem that colonizes body surfaces and interacts with host organ systems, especially the immune system. Since the composition of this ecosystem depends on a variety of internal and external factors, each individual harbors a unique set of microbes. These differences in microbiota composition make individuals either more or less susceptible to various diseases, including cancer. Specific microbes are associated with cancer etiology and pathogenesis and several mechanisms of how they drive the typical hallmarks of cancer were recently identified. Although most microbes reside in the distal gut, they can influence cancer initiation and progression in distant tissues, as well as modulate the outcomes of established cancer therapies. Here, we describe the mechanisms by which microbes influence carcinogenesis and discuss their current and potential future applications in cancer diagnostics and management.

show abstract

Section: Microbes Drive Hallmarks Of Cancermentioning

confidence: 99%

Microbiota as the unifying factor behind the hallmarks of cancer

Benešová

Křížová

Kverka

2023

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

show abstract

“…Pathogenic strains produce toxins, including colibactin, cytolethal distending toxin (CDT), cycle inhibiting factor, and cytotoxic necrotizing factor [ 67 ]. CDT is a genotoxin composed of CdtA, CdtB, and CdtC subunits [ 68 ], while the CdtB catalytic subunit might support carcinogenesis and host cell transformation in murine experiments [ 69 ]. The results from clinical studies showed that colibactin coded by Pks island was observed mainly in CRC patients [ 67 ].…”

Section: Dominant Bacteria-driven Mechanisms Associated With Cancer D...mentioning

confidence: 99%

Microbiome in Cancer Development and Treatment

Ciernikova,

Sevcikova,

Mladosievicova

et al. 2023

Microorganisms

View full text Add to dashboard Cite

Targeting the microbiome, microbiota-derived metabolites, and related pathways represents a significant challenge in oncology. Microbiome analyses have confirmed the negative impact of cancer treatment on gut homeostasis, resulting in acute dysbiosis and severe complications, including massive inflammatory immune response, mucosal barrier disruption, and bacterial translocation across the gut epithelium. Moreover, recent studies revealed the relationship between an imbalance in the gut microbiome and treatment-related toxicity. In this review, we provide current insights into the role of the microbiome in tumor development and the impact of gut and tumor microbiomes on chemo- and immunotherapy efficacy, as well as treatment-induced late effects, including cognitive impairment and cardiotoxicity. As discussed, microbiota modulation via probiotic supplementation and fecal microbiota transplantation represents a new trend in cancer patient care, aiming to increase bacterial diversity, alleviate acute and long-term treatment-induced toxicity, and improve the response to various treatment modalities. However, a more detailed understanding of the complex relationship between the microbiome and host can significantly contribute to integrating a microbiome-based approach into clinical practice. Determination of causal correlations might lead to the identification of clinically relevant diagnostic and prognostic microbial biomarkers. Notably, restoration of intestinal homeostasis could contribute to optimizing treatment efficacy and improving cancer patient outcomes.

show abstract

“…CDT and CDTB (its active subunit) are mainly produced by Campylobacter jejuni . CDT can lead to genetic instability by inducing replicative stress in several human cells (e.g., HeLa, U2OS, and RKO) and human colorectal organoids ( Tremblay et al, 2021 ). This replicative stress leads to chromosomic aberrations by slowing DNA replication and expressing fragile sites.…”

Section: The Second Hit: Dysbiosis-associated Alterations Potentiate ...mentioning

confidence: 99%

Dysbiosis: The first hit for digestive system cancer

et al. 2022

View full text Add to dashboard Cite

Gastrointestinal cancer may be associated with dysbiosis, which is characterized by an alteration of the gut microbiota. Understanding the role of gut microbiota in the development of gastrointestinal cancer is useful for cancer prevention and gut microbiota-based therapy. However, the potential role of dysbiosis in the onset of tumorigenesis is not fully understood. While accumulating evidence has demonstrated the presence of dysbiosis in the intestinal microbiota of both healthy individuals and patients with various digestive system diseases, severe dysbiosis is often present in patients with digestive system cancer. Importantly, specific bacteria have been isolated from the fecal samples of these patients. Thus, the association between dysbiosis and the development of digestive system cancer cannot be ignored. A new model describing this relationship must be established. In this review, we postulate that dysbiosis serves as the first hit for the development of digestive system cancer. Dysbiosis-induced alterations, including inflammation, aberrant immune response, bacteria-produced genotoxins, and cellular stress response associated with genetic, epigenetic, and/or neoplastic changes, are second hits that speed carcinogenesis. This review explains the mechanisms for these four pathways and discusses gut microbiota-based therapies. The content included in this review will shed light on gut microbiota-based strategies for cancer prevention and therapy.

show abstract

Cytolethal Distending Toxin Promotes Replicative Stress Leading to Genetic Instability Transmitted to Daughter Cells

Cited by 15 publications

References 51 publications

Microbiota as the unifying factor behind the hallmarks of cancer

Microbiota as the unifying factor behind the hallmarks of cancer

Microbiome in Cancer Development and Treatment

Dysbiosis: The first hit for digestive system cancer

Contact Info

Product

Resources

About