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J Infect Dis. 2014 Jul 15;210(2):285-94. doi: 10.1093/infdis/jiu071. Epub 2014 Jan 31.

The genotoxin colibactin exacerbates lymphopenia and decreases survival rate in mice infected with septicemic Escherichia coli.

Author information

1
UMR1043, Inserm USC 1360, INRA UMR 5282, CNRS UPS, Centre de Physiopathologie de Toulouse Purpan, UPS, Université de Toulouse EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
2
UMR1043, Inserm USC 1360, INRA UMR 5282, CNRS UPS, Centre de Physiopathologie de Toulouse Purpan, UPS, Université de Toulouse.
3
UMR1043, Inserm USC 1360, INRA UMR 5282, CNRS UPS, Centre de Physiopathologie de Toulouse Purpan, UPS, Université de Toulouse Neuro-gastroenterologie et Nutrition, UMR INRA/ENVT 1331.
4
UMR1043, Inserm USC 1360, INRA UMR 5282, CNRS UPS, Centre de Physiopathologie de Toulouse Purpan, UPS, Université de Toulouse Hôpital Purpan, Service de bactériologie-Hygiène, CHU Toulouse, Toulouse.

Abstract

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; colibactin; lymphonia; sepsis; toxin

PMID:
24489107
DOI:
10.1093/infdis/jiu071
[Indexed for MEDLINE]

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