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

Keshava Mysore, Limb K. Hapairai, Longhua Sun, Elizabeth I. Harper, Yingying Chen, Kathleen K. Eggleson, Jacob S. Realey, Nicholas D. Scheel, David W. Severson, Na Wei, Molly Scheel

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Although 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. Results: A 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. Conclusions: Ready-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.

Original languageEnglish (US)
Article number461
JournalMalaria Journal
Volume16
Issue number1
DOIs
StatePublished - Nov 13 2017

Fingerprint

Anopheles
Gene Targeting
Malaria
Mosquito Control
Yeasts
RNA
Mortality
Small Interfering RNA
Tablets
Saccharomyces cerevisiae
Dried Yeast
Lethal Genes
Anopheles gambiae
RNA Interference
Culicidae
Synapses
Genes
Larva
Actins
Leukocytes

Keywords

  • Brain
  • Larvae
  • Larviciding
  • Malaria
  • Mosquito
  • Pesticide
  • RNAi
  • Saccharomyces cerevisiae
  • Synapse
  • Vector

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Yeast interfering RNA larvicides targeting neural genes induce high rates of Anopheles larval mortality. / Mysore, Keshava; Hapairai, Limb K.; Sun, Longhua; Harper, Elizabeth I.; Chen, Yingying; Eggleson, Kathleen K.; Realey, Jacob S.; Scheel, Nicholas D.; Severson, David W.; Wei, Na; Scheel, Molly.

In: Malaria Journal, Vol. 16, No. 1, 461, 13.11.2017.

Research output: Contribution to journalArticle

Mysore, K, Hapairai, LK, Sun, L, Harper, EI, Chen, Y, Eggleson, KK, Realey, JS, Scheel, ND, Severson, DW, Wei, N & Scheel, M 2017, 'Yeast interfering RNA larvicides targeting neural genes induce high rates of Anopheles larval mortality', Malaria Journal, vol. 16, no. 1, 461. https://doi.org/10.1186/s12936-017-2112-5
Mysore, Keshava ; Hapairai, Limb K. ; Sun, Longhua ; Harper, Elizabeth I. ; Chen, Yingying ; Eggleson, Kathleen K. ; Realey, Jacob S. ; Scheel, Nicholas D. ; Severson, David W. ; Wei, Na ; Scheel, Molly. / Yeast interfering RNA larvicides targeting neural genes induce high rates of Anopheles larval mortality. In: Malaria Journal. 2017 ; Vol. 16, No. 1.
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AU - Sun, Longhua

AU - Harper, Elizabeth I.

AU - Chen, Yingying

AU - Eggleson, Kathleen K.

AU - Realey, Jacob S.

AU - Scheel, Nicholas D.

AU - Severson, David W.

AU - Wei, Na

AU - Scheel, Molly

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N2 - Background: Although 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. Results: A 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. Conclusions: Ready-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.

AB - Background: Although 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. Results: A 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. Conclusions: Ready-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.

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