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The Typhoid Toxin Promotes Host Survival and the Establishment of a Persistent Asymptomatic Infection
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2016 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 12, no 4, article id e1005528Article in journal (Refereed) Published
Abstract [en]

Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of these effectors during the course of infection remains poorly characterized. To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine infection. Immunocompetent mice were infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional or an inactive typhoid toxin. The presence of the genotoxic subunit was detected 10 days post-infection in the liver of infected mice. Unexpectedly, its expression promoted the survival of the host, and was associated with a significant reduction of severe enteritis in the early phases of infection. Immunohistochemical and transcriptomic analysis confirmed the toxin-mediated suppression of the intestinal inflammatory response. The presence of a functional typhoid toxin further induced an increased frequency of asymptomatic carriers. Our data indicate that the typhoid toxin DNA damaging activity increases host survival and favours long-term colonization, highlighting a complex cross-talk between infection, DNA damage response and host immune response. These findings may contribute to understand why such effectors have been evolutionary conserved and horizontally transferred among Gram-negative bacteria.

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Public Library Science , 2016. Vol. 12, no 4, article id e1005528
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Cell and Molecular Biology Infectious Medicine Cancer and Oncology Immunology Microbiology
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URN: urn:nbn:se:umu:diva-165072DOI: 10.1371/journal.ppat.1005528ISI: 000378156900023PubMedID: 27055274OAI: oai:DiVA.org:umu-165072DiVA, id: diva2:1368770
Available from: 2019-11-08 Created: 2019-11-08 Last updated: 2019-11-08Bibliographically approved

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Frisan, Teresa

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