Bacterial Genotoxin-Induced DNA Damage and Modulation of the Host Immune Microenvironment

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2020 Jan 25

PMID 31973033

Citations 23

Authors

Oceane C B Martin

Teresa Frisan

Affiliations

Soon will be listed here.

Abstract

Bacterial genotoxins (BTGX) induce DNA damage, which results in senescence or apoptosis of the target cells if not properly repaired. Three BTGXs have been identified: the cytolethal distending toxin (CDT) family produced by several Gram-negative bacteria, the typhoid toxin produced by several serovars, and colibactin, a peptide-polyketide, produced mainly by the phylogenetic group B2 . The cellular responses induced by BTGXs resemble those of well-characterized carcinogenic agents, and several lines of evidence indicate that bacteria carrying genotoxin genes can contribute to tumor development under specific circumstances. Given their unusual mode of action, it is still enigmatic why these effectors have been acquired by microbes and what is their role in the context of the biology of the producing bacterium, since it is unlikely that their primary purpose is to induce/promote cancer in the mammalian host. In this review, we will discuss the possibility that the DNA damage induced by BTGX modulates the host immune response, acting as immunomodulator, leading to the establishment of a suitable niche for the producing bacterium. We will further highlight open questions that remain to be solved regarding the biology of this unusual family of bacterial toxins.

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