Glycolysis and pyrimidine biosynthesis are required for replication of adherent–invasive escherichia coli in macrophages

Aoife P. Thompson, Ian O’Neill, Emma J. Smith, John Catchpole, Ailis Fagan, Karl E.V. Burgess, Ruaidhri J. Carmody, David J. Clarke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Adherent–invasive Escherichia coli (AIEC) have been implicated in the aetiology of Crohn’s disease (CD), a chronic inflammatory bowel condition. It has been proposed that AIEC-infected macrophages produce high levels of pro-inflammatory cytokines thus contributing to the inflammation observed in CD. AIEC can replicate in macrophages and we wanted to determine if bacterial replication was linked to the high level of cytokine production associated with AIECinfected macrophages. Therefore, we undertook a genetic analysis of the metabolic requirements for AIEC replication in the macrophage and we show that AIEC replication in this niche is dependent on bacterial glycolysis. In addition, our analyses indicate that AIEC have access to a wide range of nutrients in the macrophage, although the levels of purines and pyrimidines do appear to be limiting. Finally, we show that the macrophage response to AIEC infection is indistinguishable from the response to the non-replicating glycolysis mutant (DpfkAB) and a nonpathogenic strain of E. coli, MG1655. Therefore, AIEC does not appear to subvert the normal macrophage response to E. coli during infection.

Original languageEnglish
Article number000289
Pages (from-to)954-965
Number of pages12
JournalMicrobiology (United Kingdom)
Volume162
Issue number6
DOIs
Publication statusPublished - 1 Jun 2016

Keywords

  • AIEC
  • glycolysis
  • macrophage

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