Microbes exploit death-induced nutrient release by gut epithelial cells.

Area of Science:

• Microbiology
• Cell Biology
• Gastroenterology

Background:

• Regulated cell death is crucial for organism homeostasis, and its dysregulation is linked to gastrointestinal pathologies.
• The relationship between cell death and gut diseases with microbial involvement is known, but the direct impact of dying cells on bacterial growth remains unclear.

Purpose of the Study:

• To investigate the direct effect of dying mammalian cells on the growth of gut bacteria.
• To elucidate the mechanisms by which bacteria exploit nutrients from apoptotic cells.

Main Methods:

• Utilized primary mouse colonic tissue, mouse and human cell lines, and various apoptotic triggers.
• Employed conventional and germ-free mice for in vivo studies.
• Analyzed transcriptional responses in Salmonella and identified key genes involved in colonization.

Main Results:

• Mammalian nutrients released during caspase-3/7-dependent apoptosis significantly enhance the growth of Enterobacteriaceae.
• Identified pyruvate formate-lyase (pflB) as a critical gene for bacterial colonization in models of foodborne infection, TNF/A20-dependent cell death, and chemotherapy-induced mucositis.
• Demonstrated that dying cell nutrients induce a core transcriptional response in pathogenic Salmonella.

Conclusions:

• Dying mammalian cells release nutrients that serve as a potent fuel source for intestinal bacteria, particularly Enterobacteriaceae.
• This host-pathogen interaction provides a new perspective on gut inflammation and the impact of treatments like cytotoxic chemotherapy.