Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics
UMass Metabolic Network; Program in Systems Biology; Program in Molecular Medicine
Bacteriology | Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
The human microbiota greatly affects physiology and disease; however, the contribution of bacteria to the response to chemotherapeutic drugs remains poorly understood. Caenorhabditis elegans and its bacterial diet provide a powerful system to study host-bacteria interactions. Here, we use this system to study how bacteria affect the C. elegans response to chemotherapeutics. We find that different bacterial species can increase the response to one drug yet decrease the effect of another. We perform genetic screens in two bacterial species using three chemotherapeutic drugs: 5-fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FUDR), and camptothecin (CPT). We find numerous bacterial nucleotide metabolism genes that affect drug efficacy in C. elegans. Surprisingly, we find that 5-FU and FUDR act through bacterial ribonucleotide metabolism to elicit their cytotoxic effects in C. elegans rather than by thymineless death or DNA damage. Our study provides a blueprint for characterizing the role of bacteria in the host response to chemotherapeutics.
5-FU, C. elegans, bacteria, FUDR, camptothecin, cancer, chemotherapeutics, drug efficacy, microbiota, nucleotide metabolism
DOI of Published Version
Cell. 2017 Apr 20;169(3):431-441.e8. doi: 10.1016/j.cell.2017.03.046. Link to article on publisher's site
Garcia-Gonzalez, Aurian; Ritter, Ashlyn D.; Shrestha, Shaleen; Andersen, Erik C.; Yilmaz, L. Safak; and Walhout, Albertha J. M., "Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics" (2017). UMass Metabolic Network Publications. 69.