Caloric Restriction Mimetics, Autophagy, and Anticancer Immunosurveillance. “The bacterial metabolite prodigiosin inhibits autophagy and suppresses antitumor immunity. Results from a fluorescent biosensor-based screening of bacterial metabolites”

Nutrition plays a crucial role in the development and progression of different types of cancer. Dietary components, as well as gut microbiota-derived factors, can exert metabolic and immunomodulatory functions on the host, both locally and systemically. Recent studies highlighted the role of specific gut microbes as predictors of response to immunotherapy. Autophagy has a key function in the elicitation of an immune in response to anticancer therapy. Here, we conducted an automatized fluorescent biosensor-based screening to identify autophagy modulators from a chemical library of host- and bacteria-derived metabolites and found prodigiosin, a red pigment produced by Serratia marcescens, as a potent inducer of LC3 dots in GFP-LC3 biosensor cells. Further autophagic flux analysis in RFP-GFP-LC3 tandem reporter cells and a GFP-Q74 Huntington’s disease model revealed that prodigiosin acts as an inhibitor of autophagic flux. Consistent with the described immunosuppressive role of prodigiosin, our in vivo experiment in BALB/c mice transplanted with syngeneic colon cancers suggest that prodigiosin impairs the activity of anti-PD1 immunotherapy.