Journal Article

The Genotoxin Colibactin Exacerbates Lymphopenia and Decreases Survival Rate in Mice Infected With Septicemic <i>Escherichia coli</i>

Ingrid Marcq, Patricia Martin, Delphine Payros, Gabriel Cuevas-Ramos, Michèle Boury, Claude Watrin, Jean-Philippe Nougayrède, Maïwenn Olier and Eric Oswald

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Published in print January 2014 | ISSN: 0022-1899
Published online March 2014 | e-ISSN: 1537-6613 | DOI: https://dx.doi.org/10.1093/infdis/jiu071
The Genotoxin Colibactin Exacerbates Lymphopenia and Decreases Survival Rate in Mice Infected With Septicemic Escherichia coli

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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.

Keywords: E. coli; toxin; lymphonia; sepsis; colibactin

Journal Article.  5170 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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