Dialogue between E. coli free radical pathways and the mitochondria of C. elegans

Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):12456-61. doi: 10.1073/pnas.1517448112. Epub 2015 Sep 21.

Abstract

The microbial world presents a complex palette of opportunities and dangers to animals, which have developed surveillance and response strategies to hints of microbial intent. We show here that the mitochondrial homeostatic response pathway of the nematode Caenorhabditis elegans responds to Escherichia coli mutations that activate free radical detoxification pathways. Activation of C. elegans mitochondrial responses could be suppressed by additional mutations in E. coli, suggesting that C. elegans responds to products of E. coli to anticipate challenges to its mitochondrion. Out of 50 C. elegans gene inactivations known to mediate mitochondrial defense, we found that 7 genes were required for C. elegans response to a free radical producing E. coli mutant, including the bZip transcription factor atfs-1 (activating transcription factor associated with stress). An atfs-1 loss-of-function mutant was partially resistant to the effects of free radical-producing E. coli mutant, but a constitutively active atfs-1 mutant growing on wild-type E. coli inappropriately activated the pattern of mitochondrial responses normally induced by an E. coli free radical pathway mutant. Carbonylated proteins from free radical-producing E. coli mutant may directly activate the ATFS-1/bZIP transcription factor to induce mitochondrial stress response: feeding C. elegans with H2O2-treated E. coli induces the mitochondrial unfolded protein response, and inhibition of a gut peptide transporter partially suppressed C. elegans response to free radical damaged E. coli.

Keywords: C. elegans; host–microbe dialogue; mitochondria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Biosynthetic Pathways / genetics
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans / microbiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli / physiology
  • Free Radicals / metabolism*
  • Gene Expression
  • Host-Pathogen Interactions / genetics
  • Microscopy, Fluorescence
  • Mitochondria / metabolism*
  • Mutation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • ATFS-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Free Radicals
  • Transcription Factors