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Title [sv]
Bakteriella genotoxins: i gränssnittet mellan infektion och cancerbiologi
Title [en]
Bacterial genotoxins: an interface between infection and cancer biology
Abstract [en]
An emerging feature in commensal and pathogenic enterobacteria is the production of bacterial genotoxins, which induce DNA damage, causing cell cycle arrest, senescence or apoptosis in the host mammalian cells. These effects may significantly influence the intestinal mucosal barrier integrity, cell turnover, and microbiota composition leading to altered homeostasis and host metabolisms, and may further enhanced the susceptibility to chronic inflammatory diseases and promote carcinogenesis.The proposed project focuses on assessing the role of the bacterial genotoxin, known as typhoid toxin, in acute and chronic infections on alteration of the mucosal homeostasis, microbiota colonization and modulation of the host immune responses in the gut in in vivo, ex vivo and in vitro models.In order to exert their genotoxic activity, these bacterial effectors need to be secreted by the producing bacterium and get access to the nuclear compartment of the host cells. Thus, understanding the molecular mechanisms of internalization and intracellular trafficking represents a complementary issue to the infection models.As the Yin and Yang, the genotoxic potential of these bacterial effectors can be also exploited for anti-cancer therapy, in conjunction with the ability of bacteria to colonized solid tumors. Thus, we are developing strategies to use the non-virulent S. Typhimurium VNP20009 strain for specific tumor delivery of the genotoxic component.The characterization of the molecular mechanisms by which bacterial genotoxins contribute to chronic inflammatory conditions and eventually carcinogenesis may result in specific therapeutic protocols aimed at an early, rapid and selective eradication of bacterial populations in patients, thus preventing of the initial steps of inflammation and tumor development, promoting health and reducing the cost of cancer therapy. This study may further highlight the need to develop specific toxins? inhibitors for targeted therapy.
Principal InvestigatorFrisan, Teresa
Coordinating organisation
Umeå University
Funder
Period
2016-01-01 - 2018-12-31
National Category
Microbiology in the medical area
Identifiers
DiVA, id: project:1524Project, id: 2015-02896_VR

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