Microbes exploit death-induced nutrient release by gut epithelial cells

Christopher J. Anderson, Christopher B. Medina, Brady J. Barron, Laura Karvelyte, Tania Løve Aaes, Irina Lambertz, Justin S. A. Perry, Parul Mehrotra, Amanda Gonçalves, Kelly Lemeire, Gillian Blancke, Vanessa Andries, Farzaneh Ghazavi, Arne Martens, Geert van Loo, Lars Vereecke, Peter Vandenabeele and Kodi S. Ravichandran ()
Additional contact information
Christopher J. Anderson: VIB-UGent Center for Inflammation Research
Christopher B. Medina: University of Virginia
Brady J. Barron: University of Virginia
Laura Karvelyte: VIB-UGent Center for Inflammation Research
Tania Løve Aaes: VIB-UGent Center for Inflammation Research
Irina Lambertz: VIB-UGent Center for Inflammation Research
Justin S. A. Perry: Memorial Sloan Kettering Cancer Center
Parul Mehrotra: VIB-UGent Center for Inflammation Research
Amanda Gonçalves: VIB-UGent Center for Inflammation Research
Kelly Lemeire: VIB-UGent Center for Inflammation Research
Gillian Blancke: VIB-UGent Center for Inflammation Research
Vanessa Andries: VIB-UGent Center for Inflammation Research
Farzaneh Ghazavi: VIB-UGent Center for Inflammation Research
Arne Martens: VIB-UGent Center for Inflammation Research
Geert van Loo: VIB-UGent Center for Inflammation Research
Lars Vereecke: VIB-UGent Center for Inflammation Research
Peter Vandenabeele: VIB-UGent Center for Inflammation Research
Kodi S. Ravichandran: VIB-UGent Center for Inflammation Research

Nature, 2021, vol. 596, issue 7871, 262-267

Abstract: Abstract Regulated cell death is an integral part of life, and has broad effects on organism development and homeostasis1. Malfunctions within the regulated cell death process, including the clearance of dying cells, can manifest in diverse pathologies throughout various tissues including the gastrointestinal tract2. A long appreciated, yet elusively defined relationship exists between cell death and gastrointestinal pathologies with an underlying microbial component3–6, but the direct effect of dying mammalian cells on bacterial growth is unclear. Here we advance a concept that several Enterobacteriaceae, including patient-derived clinical isolates, have an efficient growth strategy to exploit soluble factors that are released from dying gut epithelial cells. Mammalian nutrients released after caspase-3/7-dependent apoptosis boosts the growth of multiple Enterobacteriaceae and is observed using primary mouse colonic tissue, mouse and human cell lines, several apoptotic triggers, and in conventional as well as germ-free mice in vivo. The mammalian cell death nutrients induce a core transcriptional response in pathogenic Salmonella, and we identify the pyruvate formate-lyase-encoding pflB gene as a key driver of bacterial colonization in three contexts: a foodborne infection model, a TNF- and A20-dependent cell death model, and a chemotherapy-induced mucositis model. These findings introduce a new layer to the complex host–pathogen interaction, in which death-induced nutrient release acts as a source of fuel for intestinal bacteria, with implications for gut inflammation and cytotoxic chemotherapy treatment.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03785-9 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:596:y:2021:i:7871:d:10.1038_s41586-021-03785-9

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03785-9

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().