Bacterial genotoxin functions as immune-modulator and promotes host survival

Bacterial genotoxins are effectors that cause DNA damage in target cells. Many aspects of the biology of these toxins have been characterised in vitro, such as structure, cellular internalisation pathways and effects on the target cells. However, little is known about their function in vivo. Salmone...

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Main Authors: Riccardo Guidi, L. Del Bell Belluz, T. Frisan
Format: Article
Language:English
Published: Shared Science Publishers OG 2016-07-01
Series:Microbial Cell
Subjects:
Online Access:http://microbialcell.com/researcharticles/bacterial-genotoxin-functions-as-immune-modulator-and-promotes-host-survival/
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author Riccardo Guidi
L. Del Bell Belluz
T. Frisan
author_facet Riccardo Guidi
L. Del Bell Belluz
T. Frisan
author_sort Riccardo Guidi
collection DOAJ
description Bacterial genotoxins are effectors that cause DNA damage in target cells. Many aspects of the biology of these toxins have been characterised in vitro, such as structure, cellular internalisation pathways and effects on the target cells. However, little is known about their function in vivo. Salmonella enterica serovar Typhi (S. Typhi) is a Gram-negative, intracellular bacterium that causes typhoid fever, a debilitating disease infecting more than 20 million people every year. S. Typhi produce a genotoxin named typhoid toxin (TT), but its role in the contest of host infection is poorly characterized. The major obstacle in addressing this issue is that S. Typhi is exclusively a human pathogen. To overcome this limitation, we have used as model bacterium S. Typhimurium, and engineered it to produce endogenous levels of an active and inactive typhoid toxin, hereby named as TT (or genotoxic) and cdtB (or control), respectively. To our surprise, infection with the genotoxin strain strongly suppressed intestinal inflammation, leading to a better survival of the host during the acute phase of infection, suggesting typhoid toxin may exert a protective role. The presence of a functional genotoxin was also associated with an increased frequency of asymptomatic carriers.
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spelling doaj.art-d8cc263669f0437d98bf06e11c9b98fb2022-12-22T02:46:36ZengShared Science Publishers OGMicrobial Cell2311-26382016-07-013835535710.15698/mic2016.08.520Bacterial genotoxin functions as immune-modulator and promotes host survivalRiccardo Guidi0L. Del Bell Belluz1T. Frisan2The Laboratory of Allergy and Anti-Helminth Immunity, The Francis Crick Institute, London, UK.Dept. of Cell and Molecular Biology, Karolinska Institute, Stockholm Sweden.Dept. of Cell and Molecular Biology, Karolinska Institute, Stockholm Sweden.Bacterial genotoxins are effectors that cause DNA damage in target cells. Many aspects of the biology of these toxins have been characterised in vitro, such as structure, cellular internalisation pathways and effects on the target cells. However, little is known about their function in vivo. Salmonella enterica serovar Typhi (S. Typhi) is a Gram-negative, intracellular bacterium that causes typhoid fever, a debilitating disease infecting more than 20 million people every year. S. Typhi produce a genotoxin named typhoid toxin (TT), but its role in the contest of host infection is poorly characterized. The major obstacle in addressing this issue is that S. Typhi is exclusively a human pathogen. To overcome this limitation, we have used as model bacterium S. Typhimurium, and engineered it to produce endogenous levels of an active and inactive typhoid toxin, hereby named as TT (or genotoxic) and cdtB (or control), respectively. To our surprise, infection with the genotoxin strain strongly suppressed intestinal inflammation, leading to a better survival of the host during the acute phase of infection, suggesting typhoid toxin may exert a protective role. The presence of a functional genotoxin was also associated with an increased frequency of asymptomatic carriers.http://microbialcell.com/researcharticles/bacterial-genotoxin-functions-as-immune-modulator-and-promotes-host-survival/genotoxinSalmonellatyphoid toxinDNA damage inflammationpersistent infection
spellingShingle Riccardo Guidi
L. Del Bell Belluz
T. Frisan
Bacterial genotoxin functions as immune-modulator and promotes host survival
Microbial Cell
genotoxin
Salmonella
typhoid toxin
DNA damage
inflammation
persistent infection
title Bacterial genotoxin functions as immune-modulator and promotes host survival
title_full Bacterial genotoxin functions as immune-modulator and promotes host survival
title_fullStr Bacterial genotoxin functions as immune-modulator and promotes host survival
title_full_unstemmed Bacterial genotoxin functions as immune-modulator and promotes host survival
title_short Bacterial genotoxin functions as immune-modulator and promotes host survival
title_sort bacterial genotoxin functions as immune modulator and promotes host survival
topic genotoxin
Salmonella
typhoid toxin
DNA damage
inflammation
persistent infection
url http://microbialcell.com/researcharticles/bacterial-genotoxin-functions-as-immune-modulator-and-promotes-host-survival/
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