Τίτλος:
The Typhoid Toxin Promotes Host Survival and the Establishment of a Persistent Asymptomatic Infection
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2016 Del Bel Belluz et al.
Συγγραφείς:
Del Bel Belluz, L.
Guidi, R.
Pateras, I.S.
Levi, L.
Mihaljevic, B.
Rouf, S.F.
Wrande, M.
Candela, M.
Turroni, S.
Nastasi, C.
Consolandi, C.
Peano, C.
Tebaldi, T.
Viero, G.
Gorgoulis, V.G.
Krejsgaard, T.
Rhen, M.
Frisan, T.
Περιοδικό:
PLoS Pathogens
Εκδότης:
Public Library of Science
Λέξεις-κλειδιά:
bacterial toxin; CD45 antigen; cytolethal distending toxin; transcriptome; typhoid toxin; unclassified drug; virulence factor; mutagenic agent, animal model; animal tissue; antigen expression; Article; asymptomatic infection; bacterial colonization; bacterial load; bacterial virulence; controlled study; DNA damage; enteritis; female; gene amplification; gene expression; immune response; immunocompetence; immunohistochemistry; immunomodulation; inflammation; intestine flora; microbial diversity; mouse; nonhuman; polymerase chain reaction; Salmonella enterica; typhoid fever; animal; communicable disease; intestine; macrophage; microbiology; pathogenicity; Salmonella enterica serovar Typhimurium; typhoid fever; virulence, Animals; Asymptomatic Infections; Communicable Diseases; Intestines; Macrophages; Mice; Mutagens; Salmonella typhimurium; Typhoid Fever; Virulence
DOI:
10.1371/journal.ppat.1005528
