Initial Characterization of Corticosteroid-Metabolizing Enzymes Found in Human Gut Bacteria
Subject Area
Biology; Chemistry
Description
Jackson DeMartino ’23, Major: Biochemistry
Lily Lockhart ’22, Major: Biochemistry
Kailey Paar ’23, Major: Biochemistry
Faculty Mentor: Dr. Tyler Stack, Chemistry and Biochemistry
Individuals have varied responses to drug therapies, which can be costly and dangerous due to treatment delays and adverse side effects. Personalized medicine aims to address this issue, which will depend on an individual's genome. However, the specific molecular mechanisms by which gut microbes metabolize drugs receive much less attention, and the heterogeneity between individual gut microbiomes further complicates the matter. To address this problem, we have targeted several proteins found in human gut microbes, including Eggerthella lenta, Clostridium scindens, and Eubacterium desmolans, to test their ability to metabolize and alter drug structures. These enzymes include hydroxysteroid dehydrogenases and cortisol desmolase, which alter the structure of host-produced steroids. Thus, we hypothesized that these enzymes affect drug metabolism on therapeutics designed to mimic cortisol structurally (corticosteroids). In this project, we have cloned, produced, and tested the metabolizing activity of some steroid dehydrogenases and desmolases. Our future goal is to begin to identify and quantify the efficiency of these drug-metabolizing enzymes. This investigation serves as a springboard into how a unique community of gut microbes modifies therapeutics, which can help predict drug metabolism based on an individual’s microbiome.
Publisher
Providence College
Date
4-26-2022
Type
Poster
Language
English
