Effective drug combination for Caenorhabditis elegans nematodes discovered by output-driven feedback system control technique

• DOI: 10.1126/sciadv.aao1254
• Publication Date: 2017-10-05T01:00:33Z
• Authors: Xianting Ding; Zach Njus; Taejoon Kong; Wenqiong Su; Chih-Ming Ho; Santosh Pandey
• Keywords: Anthelmintics; 570; Dose-Response Relationship, Drug; Image and Video Processing (eess.IV); Systems and Control (eess.SY); Electrical Engineering and Systems Science - Image and Video Processing; Quantitative Biology - Quantitative Methods; Electrical Engineering and Systems Science - Systems and Control; 3. Good health; Parasitic Sensitivity Tests; FOS: Biological sciences; Drug Discovery; FOS: Electrical engineering, electronic engineering, information engineering; Animals; Humans; Drug Therapy, Combination; Caenorhabditis elegans; Research Articles; Quantitative Methods (q-bio.QM)

Infections from parasitic nematodes (or roundworms) contribute to a significant disease burden and productivity losses for humans livestock. The limited number of anthelmintics antinematode drugs) available today treat these infections are rapidly losing their efficacy as multidrug resistance in parasites becomes global health challenge. We propose an engineering approach discover anthelmintic drug combination that is more potent at killing wild-type Caenorhabditis elegans worms than four individual drugs. In the experiment, freely swimming single enclosed microfluidic environments assess centroid velocity track curvature worm movements. After analyzing behavioral data every iteration, feedback system control (FSC) scheme used predict new combinations test. Through differential evolutionary search, winning reached produces minimal high curvature, while requiring each less EC50 concentrations. FSC model-less does not need any information on pharmacology, signaling pathways, or animal biology. Toward combating resistance, method presented here applicable discovery C. elegans, nematodes, other small model organisms.