The genotoxin Colibactin exacerbates lymphopenia and decreases survival rate in mice infected with septicemic Escherichia coli
| Autor: | Delphine Payros, Patricia Martin, Ingrid Marcq, Jean-Philippe Nougayrède, Maïwenn Olier, Michèle Boury, Eric Oswald, Gabriel Cuevas-Ramos, Claude Watrin |
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| Přispěvatelé: | ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Lymphocyte
[SDV]Life Sciences [q-bio] Antibiotics medicine.disease_cause Mice Immunology and Allergy EPIDEMIOLOGY DNA Breaks Double-Stranded Lymphocytes toxin Escherichia coli Infections 0303 health sciences Extraintestinal Pathogenic Escherichia coli IMPROVES SURVIVAL IMMUNOSUPPRESSION Cell Death Virulence 3. Good health APOPTOSIS LYMPHOCYTE Infectious Diseases medicine.anatomical_structure Female colibactin Programmed cell death Virulence Factors medicine.drug_class PATHOPHYSIOLOGY Biology Microbiology Sepsis 03 medical and health sciences lymphonia Lymphopenia Escherichia coli medicine Animals 030304 developmental biology SEPSIS 030306 microbiology E. coli medicine.disease Survival Analysis [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Virology Mice Inbred C57BL CELL-DEATH Polyketides Bacteremia Peptides Gene Deletion CD4(+) Mutagens RESPONSES |
| Zdroj: | Journal of Infectious Diseases Journal of Infectious Diseases, Oxford University Press (OUP), 2014, 210 (2), pp.285-294. ⟨10.1093/infdis/jiu071⟩ |
| ISSN: | 0022-1899 1537-6613 |
| DOI: | 10.1093/infdis/jiu071⟩ |
| Popis: | International audience; Sepsis is a life-threatening infection. Escherichia coli is the first known cause of bacteremia leading to sepsis. Lymphopenia was shown to predict bacteremia better than conventional markers of infection. The pks genomic island, which is harbored by extraintestinal pathogenic E. coli (ExPEC) and encodes the genotoxin colibactin, is epidemiologically associated with bacteremia. To investigate a possible relationship between colibactin and lymphopenia, we examined the effects of transient infection of lymphocytes with bacteria that were and those that were not producing the genotoxin. A mouse model of sepsis was used to compare the virulence of a clinical ExPEC isolate with its isogenic mutant impaired for the production of colibactin. We observed that colibactin induced double-strand breaks in the DNA of infected lymphocytes, leading to cell cycle arrest and to cell death by apoptosis. E. coli producing colibactin induced a more profound lymphopenia in septicemic mice, compared with the isogenic mutant unable to produce colibactin. In a sepsis model in which the mice were treated by rehydration and antibiotics, the production of colibactin by the bacteria was associated with a significantly lower survival rate. In conclusion, we demonstrate that production of colibactin by E. coli exacerbates lymphopenia associated with septicemia and could impair the chances to survive sepsis. |
| Databáze: | OpenAIRE |
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