Yeast interfering RNA larvicides targeting neural genes induce high rates of Anopheles larval mortality

Malaria Journal

Research

Keshava Mysore¹  Limb K. Hapairai¹  Jacob S. Realey¹  Elizabeth I. Harper¹  Molly Duman-Scheel²  David W. Severson²  Nicholas D. Scheel³  Longhua Sun³  Na Wei⁴  Yingying Chen⁴  Kathleen K. Eggleson⁵ 

[1] Dept. of Medical and Molecular Genetics, Indiana University School of Medicine, 1234 Notre Dame Avenue, 46530, South Bend, IN, USA;The University of Notre Dame, Eck Institute for Global Health, 46556, Notre Dame, IN, USA;Dept. of Medical and Molecular Genetics, Indiana University School of Medicine, 1234 Notre Dame Avenue, 46530, South Bend, IN, USA;The University of Notre Dame, Eck Institute for Global Health, 46556, Notre Dame, IN, USA;Dept. of Biological Sciences, The University of Notre Dame, 46556, Notre Dame, IN, USA;The University of Notre Dame, Eck Institute for Global Health, 46556, Notre Dame, IN, USA;Dept. of Biological Sciences, The University of Notre Dame, 46556, Notre Dame, IN, USA;The University of Notre Dame, Eck Institute for Global Health, 46556, Notre Dame, IN, USA;Dept. of Civil and Environmental Engineering and Earth Sciences, The University of Notre Dame, 46556, Notre Dame, IN, USA;The University of Notre Dame, Eck Institute for Global Health, 46556, Notre Dame, IN, USA;Dept. of Medicine, Indiana University School of Medicine, 1234 Notre Dame Avenue, 46530, South Bend, IN, USA;

关键词: Mosquito;    Vector;    Malaria;    RNAi;    Saccharomyces cerevisiae;    Larviciding;    Pesticide;    Synapse;    Brain;    Larvae;   

DOI  :  10.1186/s12936-017-2112-5

 received in 2017-07-11, accepted in 2017-11-08,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAlthough larviciding can reduce the number of outdoor biting malaria vector mosquitoes, which may help to prevent residual malaria transmission, the current larvicide repertoire is faced with great challenges to sustainability. The identification of new effective, economical, and biorational larvicides could facilitate maintenance and expansion of the practice of larviciding in integrated malaria vector mosquito control programmes. Interfering RNA molecules represent a novel class of larvicides with untapped potential for sustainable mosquito control. This investigation tested the hypothesis that short interfering RNA molecules can be used as mosquito larvicides.ResultsA small interfering RNA (siRNA) screen for larval lethal genes identified siRNAs corresponding to the Anopheles gambiae suppressor of actin (Sac1), leukocyte receptor complex member (lrc), and offtrack (otk) genes. Saccharomyces cerevisiae (baker’s yeast) was engineered to produce short hairpin RNAs (shRNAs) for silencing of these genes. Feeding larvae with the engineered yeasts resulted in silenced target gene expression, a severe loss of neural synapses in the larval brain, and high levels of larval mortality. The larvicidal activities of yeast interfering RNA larvicides were retained following heat inactivation and drying of the yeast into user-friendly tablet formulations that induced up to 100% larval mortality in laboratory trials.ConclusionsReady-to-use dried inactivated yeast interfering RNA larvicide tablets may someday be an effective and inexpensive addition to malaria mosquito control programmes and a valuable, biorational tool for addressing residual malaria transmission.

【 授权许可】

CC BY   
© The Author(s) 2017