Death induced nutrient release fuels bacterial growth

01 October 2020 → 31 March 2023
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Inflammation
    • Innate immunity
    • Bacteriology
    • Infectious diseases
    • Bacteriology
apoptosis microbiology infection
Project description

Billions of cells die and must be efficiently cleared from the body on a daily basis to ensure normal tissue development and homeostasis. As part of normal homeostatic death, apoptotic cells release a wide variety of molecules in a regulated manner, including lysine and polyamines. My data indicate that dying mammalian cells produce a ‘bioactive’ supernatant that directly enhances the growth of foodborne bacterial pathogens and opportunistic pathogens within the microbiota. I have developed highly adaptable in vitro and ex vivo models of immortalized and primary colonocyte cell death to test the impact of caspase dependent death induced nutrient release on bacterial physiology. Using these models, I identified robust upregulation of bacterial lysine and polyamine transport systems. I will further elucidate the consequences of intestinal epithelial cell death on pathogen growth in vivo, and uncover the bacterial and mammalian factors responsible for apoptosis driven bacterial outgrowth. Finally, I will investigate the contribution of death induced nutrient release during inflammatory bowel disease. This proposal is poised to make novel and meaningful contributions to the fields of infectious disease and inflammatory bowel disease research. Findings from this work may lead to novel therapeutic strategies that will seek to limit the availability of these nutrients that preferentially select for pathogen growth and contribute to patient susceptibility to infection.