title: Bacterial genotoxin functions as immune-modulator and promotes host survival.
abstract: Bacterial genotoxins are effectors that cause DNA damage in target cells. Many aspects of the biology of these toxins have been characterisedin vitro, such as structure, cellular internalisation pathways and effects on the target cells. However, little is known about their functionin vivo.Salmonella entericaserovar 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.Typhiproduce 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 thatS.Typhi is exclusively a human pathogen. To overcome this limitation, we have used as model bacteriumS.Typhimurium, and engineered it to produce endogenous levels of an active and inactive typhoid toxin, hereby named as TT (or genotoxic) andcdtB(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.
authors.affiliation: The Laboratory of Allergy and Anti-Helminth Immunity, The Francis Crick Institute, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Guidi
authors.affiliation: Dept. of Cell and Molecular Biology, Karolinska Institute, Stockholm Sweden.
authors.forename: L Del Bell
authors.initials: LD
authors.lastname: Belluz
authors.affiliation: Dept. of Cell and Molecular Biology, Karolinska Institute, Stockholm Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Frisan
keywords: DNA damage; Salmonella; genotoxin; inflammation; persistent infection; typhoid toxin