Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2017 Apr 22

PMID 28431244

Citations 132

Authors

Aurian P Garcia-Gonzalez

Ashlyn D Ritter

Shaleen Shrestha

Erik C Andersen

L Safak Yilmaz

Albertha J M Walhout

Affiliations

Soon will be listed here.

Abstract

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.

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