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Microbes exploit death-induced nutrient release by gut epithelial cells

(2021) NATURE. 596(7871). p.262-267
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Abstract
Regulated cell death is an integral part of life, and has broad effects on organism development and homeostasis(1). Malfunctions within the regulated cell death process, including the clearance of dying cells, can manifest in diverse pathologies throughout various tissues including the gastrointestinal tract(2). A long appreciated, yet elusively defined relationship exists between cell death and gastrointestinal pathologies with an underlying microbial component(3-6), 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.
Keywords
ESCHERICHIA-COLI, SALMONELLA, APOPTOSIS, DYSBIOSIS, INFLAMMATION, HOMEOSTASIS, INFECTION, TOXICITY, BACTERIA, CHANNELS

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Citation

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MLA
Anderson, Christopher, et al. “Microbes Exploit Death-Induced Nutrient Release by Gut Epithelial Cells.” NATURE, vol. 596, no. 7871, 2021, pp. 262–67, doi:10.1038/s41586-021-03785-9.
APA
Anderson, C., Medina, C. B., Barron, B. J., Karvelyte, L., Aaes, T. L., Lambertz, I., … Ravichandran, K. (2021). Microbes exploit death-induced nutrient release by gut epithelial cells. NATURE, 596(7871), 262–267. https://doi.org/10.1038/s41586-021-03785-9
Chicago author-date
Anderson, Christopher, Christopher B. Medina, Brady J. Barron, Laura Karvelyte, Tania Love Aaes, Irina Lambertz, Justin S. A. Perry, et al. 2021. “Microbes Exploit Death-Induced Nutrient Release by Gut Epithelial Cells.” NATURE 596 (7871): 262–67. https://doi.org/10.1038/s41586-021-03785-9.
Chicago author-date (all authors)
Anderson, Christopher, Christopher B. Medina, Brady J. Barron, Laura Karvelyte, Tania Love 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 Ravichandran. 2021. “Microbes Exploit Death-Induced Nutrient Release by Gut Epithelial Cells.” NATURE 596 (7871): 262–267. doi:10.1038/s41586-021-03785-9.
Vancouver
1.
Anderson C, Medina CB, Barron BJ, Karvelyte L, Aaes TL, Lambertz I, et al. Microbes exploit death-induced nutrient release by gut epithelial cells. NATURE. 2021;596(7871):262–7.
IEEE
[1]
C. Anderson et al., “Microbes exploit death-induced nutrient release by gut epithelial cells,” NATURE, vol. 596, no. 7871, pp. 262–267, 2021.
@article{8712329,
  abstract     = {{Regulated cell death is an integral part of life, and has broad effects on organism development and homeostasis(1). Malfunctions within the regulated cell death process, including the clearance of dying cells, can manifest in diverse pathologies throughout various tissues including the gastrointestinal tract(2). A long appreciated, yet elusively defined relationship exists between cell death and gastrointestinal pathologies with an underlying microbial component(3-6), 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.}},
  author       = {{Anderson, Christopher and Medina, Christopher B. and Barron, Brady J. and Karvelyte, Laura and Aaes, Tania Love and Lambertz, Irina and Perry, Justin S. A. and Mehrotra, Parul and Gonçalves, Amanda and Lemeire, Kelly and Blancke, Gillian and Andries, Vanessa and Ghazavi, Farzaneh and Martens, Arne and van Loo, Geert and Vereecke, Lars and Vandenabeele, Peter and Ravichandran, Kodi}},
  issn         = {{0028-0836}},
  journal      = {{NATURE}},
  keywords     = {{ESCHERICHIA-COLI,SALMONELLA,APOPTOSIS,DYSBIOSIS,INFLAMMATION,HOMEOSTASIS,INFECTION,TOXICITY,BACTERIA,CHANNELS}},
  language     = {{eng}},
  number       = {{7871}},
  pages        = {{262--267}},
  title        = {{Microbes exploit death-induced nutrient release by gut epithelial cells}},
  url          = {{http://dx.doi.org/10.1038/s41586-021-03785-9}},
  volume       = {{596}},
  year         = {{2021}},
}

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