What is it about?
This study proposes an engineering-based solution to fight the global health challenge of multidrug resistance in parasitic nematodes. By using freely swimming worms enclosed in microfluidic drug environments and the feedback system control (FSC) scheme, a more potent combination of anthelmintic drugs is discovered that is better at killing wild-type Caenorhabditis elegans worms than four individual drugs. The winning drug combination is found to require less than their EC50 concentrations and produces minimal centroid velocity and high track curvature. This FSC approach does not need any information on the drug pharmacology, signaling pathways, or animal biology and can be used to find new combinations of existing anthelmintics not only on C. elegans, but also on other parasitic nematodes and small model organisms.
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Why is it important?
Parasitic nematodes, or roundworms, contribute to significant disease and economic losses for humans and livestock. Currently available anthelmintics, or antinematode drugs, are rapidly becoming ineffective due to multidrug resistance. To address this challenge, we use an engineering approach to discover a drug combination that is more effective than four individual drugs.
Perspectives
A microfluidic drug environment is used to assess the centroid velocity and track curvature of freely swimming worms. Applying a feedback system control (FSC) scheme and a differential evolutionary search, we find a winning drug combination that produces minimal centroid velocity and high track curvature, while using each drug in less than their EC50 concentrations. This model-less approach does not require any knowledge of drug pharmacology, signaling pathways, or animal biology. Our method is applicable to the discovery of new potent combinations of anthelmintics on C. elegans, parasitic nematodes, and other small model organisms that could combat multidrug resistance.
Prof Santosh Pandey
Iowa State University
Read the Original
This page is a summary of: Effective drug combination for
Caenorhabditis elegans
nematodes discovered by output-driven feedback system control technique, Science Advances, October 2017, American Association for the Advancement of Science,
DOI: 10.1126/sciadv.aao1254.
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