Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics
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Authors
Garcia-Gonzalez, AurianRitter, Ashlyn D.
Shrestha, Shaleen
Andersen, Erik C.
Yilmaz, L. Safak
Walhout, Albertha J. M.
UMass Chan Affiliations
Program in Molecular MedicineProgram in Systems Biology
UMass Metabolic Network
Document Type
Journal ArticlePublication Date
2017-04-20Keywords
5-FUC. elegans
bacteria
FUDR
camptothecin
cancer
chemotherapeutics
drug efficacy
microbiota
nucleotide metabolism
Bacteriology
Biochemistry
Cell Biology
Cellular and Molecular Physiology
Molecular Biology
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Show full item recordAbstract
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.Source
Cell. 2017 Apr 20;169(3):431-441.e8. doi: 10.1016/j.cell.2017.03.046. Link to article on publisher's siteDOI
10.1016/j.cell.2017.03.046Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36700PubMed ID
28431244Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2017.03.046