The Typhoid Toxin Promotes Host Survival and the Establishment of a Persistent Asymptomatic Infection

PLoS Pathogens

Thorbjørn Krejsgaard¹  Toma Tebaldi²  Laura Levi³  Riccardo Guidi³  Lisa Del Bel Belluz³  Boris Mihaljevic³  Vassilis G. Gorgoulis⁴  Ioannis S. Pateras⁴  Claudia Nastasi⁵  Syed Fazle Rouf⁶  Marie Wrande⁶  Silvia Turroni⁷  Marco Candela⁷  Mikael Rhen⁸  Clelia Peano⁹  Clarissa Consolandi⁹  Gabriella Viero^1,10  Teresa Frisan^1,11 

[1] Biomedical Research Foundation, Academy of Athens, Athens, Greece;Centre for Integrative Biology University of Trento, Trento, Italy;Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden;Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece;Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden;Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy;Institute for Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom;Institute of Biomedical Technologies, Italian National Research Council, Segrate, Milan, Italy;Institute of Biophysics of CNR, Trento, Italy;Manchester Centre for Cellular Metabolism, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom

关键词: Toxins;    Typhoid;    Salmonella typhimurium;    Gastrointestinal tract;    Salmonellosis;    Mouse models;    Colon;    DNA damage;   

DOI  :  10.1371/journal.ppat.1005528

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY