A novel isothermal microcalorimetry tool to assess drug effects on Ancylostoma ceylanicum and Necator americanus

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• 作者：Dayana Flores ; Gordana Panic ; Olivier Braissant…
• 关键词：Drug screening ; Drug discovery ; Hookworm ; Isothermal microcalorimetry ; Whipworm
• 刊名：Applied Microbiology and Biotechnology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：100
• 期：2
• 页码：837-846
• 全文大小：1,168 KB
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• 作者单位：Dayana Flores (1) (2)
  Gordana Panic (1) (2)
  Olivier Braissant (3)
  Jennifer Keiser (1) (2)
  
  1. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002, Basel, Switzerland
  2. University of Basel, CH-4003, Basel, Switzerland
  3. Center of Biomechanics & Biocalorimetry, University of Basel c/o Department Biomedical Engineering (DBE), CH-4123, Allschwil, Switzerland
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Biotechnology
  Microbiology
  Microbial Genetics and Genomics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0614

文摘

Soil-transmitted helminths, which affect the poorest communities, worldwide cause a range of symptoms and morbidity, yet few treatment options are available and drug resistance is a concern. To improve and accelerate anthelminthic drug discovery, novel drug screening tools such as isothermal microcalorimetry (IMC) have been tested with great potential. In this study, we used a novel microcalorimeter, the calScreener™, to study the viability on the hookworms Necator americanus and Ancylostoma ceylanicum as well as the whipworm Trichuris muris. Significant heat flow signals could be obtained with already one adult worm per channel for all three species. High-amplitude oscillations were observed for the hookworms; however, adult T. muris showed a twofold heat flow decrease during the first 24 h. Antinematodal effects of ivermectin and levamisole at 1, 10, and 100 μg/ml were evaluated on adult N. americanus and A. ceylanicum. Levamisole-treated hookworms showed a decline in heat flow and oscillation amplitude in a dose-response manner. Heat flow for ivermectin-treated hookworms increased proportionally with increased concentrations of ivermectin, though the wavelet analysis showed an opposite trend as observed by flatter wavelets. In conclusion, the calScreener™ is an excellent tool to study drug effects on intestinal hookworms at the adult worm stage as it offers a lower detection limit than other IMC devices and the possibility to monitor worm viability online. Keywords Drug screening Drug discovery Hookworm Isothermal microcalorimetry Whipworm