Article
Effective drug combination for Caenorhabditis elegans nematodes discovered by output-driven feedback system control technique
Science Advances
(2017)
Abstract
Infections from parasitic nematodes (or roundworms) contribute to a significant disease burden and productivity losses for humans and livestock. The limited number of anthelmintics (or antinematode drugs) available today to treat these infections are rapidly losing their efficacy as multidrug resistance in parasites becomes a global health challenge. We propose an engineering approach to discover an anthelmintic drug combination that is more potent at killing wild-type Caenorhabditis elegans worms than four individual drugs. In the experiment, freely swimming single worms are enclosed in microfluidic drug environments to assess the centroid velocity and track curvature of worm movements. After analyzing the behavioral data in every iteration, the feedback system control (FSC) scheme is used to predict new drug combinations to test. Through a differential evolutionary search, the winning drug combination is reached that produces minimal centroid velocity and high track curvature, while requiring each drug in less than their EC50 concentrations. The FSC approach is model-less and does not need any information on the drug pharmacology, signaling pathways, or animal biology. Toward combating multidrug resistance, the method presented here is applicable to the discovery of new potent combinations of available anthelmintics on C. elegans, parasitic nematodes, and other small model organisms.
Keywords
- antibiotics,
- c. elegans,
- drug screening,
- drug combination,
- combinatorial chemistry,
- drug,
- dose response,
- feedback control,
- anti nematode drug,
- anti parasitic drug
Disciplines
Publication Date
October, 2017
DOI
10.1126/sciadv.aao1254
Citation Information
Ding X, Njus Z, Kong T, Su W, Ho CM, Pandey S. Effective drug combination for Caenorhabditis elegans nematodes discovered by output-driven feedback system control technique. Sci Adv. 2017 Oct 4;3(10):eaao1254. doi: 10.1126/sciadv.aao1254. PMID: 28983514; PMCID: PMC5627981.