The bacteria that live in our body (microbiota) help us metabolize different nutrients and chemicals from our diet, including the medications we take. Thus, these bacteria can influence our response to treatments, like chemotherapy, by converting drugs into more or less toxic forms. Understanding the mechanisms by which bacteria influence our response to drugs is critical to design better treatments that maximize therapeutic effects and minimize adverse effects. The nematode C. elegans and its bacterial diet provide a suitable model to explore host-microbe drug interactions because both host and microbe are amenable to high throughput drug screening and genetic screening. I propose to use the nematode C. elegans as a model to study host-microbe-drug interactions in cancer chemotherapy drugs.
In Aim 1, I will test ~ 200 cancer chemotherapy drugs for developmental or fecundity phenotypes in C. elegans animals fed two different bacteria. Additionally, I will test the role of active bacterial metabolism in the observed host-microbe-drug interactions. Then, I will use genetic screening and metabolomics, in the host and in the bacteria, to characterize the mechanisms responsible for the observed drug response. In summary, this project will generate a set of host and bacterial genes that contribute to the response to cancer chemotherapeutic agents.
Bacteria and other microorganisms influence our overall health, our metabolism and our propensity for diseases. However, we understand very little about the mechanisms by which bacteria influence our metabolism, including the way our bodies metabolize medications. This project will provide important insight into the mechanisms by which bacteria influence the response to cancer chemotherapy drugs.
|García-González, Aurian P; Ritter, Ashlyn D; Shrestha, Shaleen et al. (2017) Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics. Cell 169:431-441.e8|