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

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.

• Authors: Ingrid Marcq, Patricia Martin, Delphine Payros, Gabriel Cuevas-Ramos, Michèle Boury, Claude Watrin, Jean-Philippe Nougayrède, Maïwenn Olier, Eric Oswald
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 210 Issue 2 Pg. 285-94 (Jul 15 2014) ISSN: 1537-6613 [Electronic] United States
• PMID: 24489107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Mutagens
• Peptides
• Polyketides
• Virulence Factors
• colibactin

Topics

• Animals
• Cell Death
• DNA Breaks, Double-Stranded
• Escherichia coli (pathogenicity)
• Escherichia coli Infections (complications, pathology)
• Female
• Gene Deletion
• Lymphocytes (microbiology, physiology)
• Lymphopenia (chemically induced)
• Mice
• Mice, Inbred C57BL
• Mutagens (toxicity)
• Peptides (genetics, toxicity)
• Polyketides (toxicity)
• Sepsis (complications, pathology)
• Survival Analysis
• Virulence
• Virulence Factors (genetics, toxicity)