Activation of akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in anopheles stephensi mosquitoes

Vanessa Corby-Harris, Anna Drexler, Laurel Watkins de Jong, Yevgeniya Antonova, Nazzy Pakpour, Rolf Ziegler, Frank Ramberg, Edwin E. Lewis, Jessica M. Brown, Shirley Luckhart, Michael A. Riehle

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Malaria (Plasmodium spp.) kills nearly one million people annually and this number will likely increase as drug and insecticide resistance reduces the effectiveness of current control strategies. The most important human malaria parasite, Plasmodium falciparum, undergoes a complex developmental cycle in the mosquito that takes approximately two weeks and begins with the invasion of the mosquito midgut. Here, we demonstrate that increased Akt signaling in the mosquito midgut disrupts parasite development and concurrently reduces the duration that mosquitoes are infective to humans. Specifically, we found that increased Akt signaling in the midgut of heterozygous Anopheles stephensi reduced the number of infected mosquitoes by 60-99%. Of those mosquitoes that were infected, we observed a 75-99% reduction in parasite load. In homozygous mosquitoes with increased Akt signaling parasite infection was completely blocked. The increase in midgut-specific Akt signaling also led to an 18-20% reduction in the average mosquito lifespan. Thus, activation of Akt signaling reduced the number of infected mosquitoes, the number of malaria parasites per infected mosquito, and the duration of mosquito infectivity.

Original languageEnglish (US)
Article numbere1001003
Pages (from-to)1-10
Number of pages10
JournalPLoS Pathogens
Volume6
Issue number7
DOIs
StatePublished - Jul 2010

Fingerprint

Parasitic Diseases
Anopheles
Culicidae
Malaria
Parasites
Plasmodium malariae
Parasite Load
Insecticide Resistance
Falciparum Malaria
Drug Resistance

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Corby-Harris, V., Drexler, A., de Jong, L. W., Antonova, Y., Pakpour, N., Ziegler, R., ... Riehle, M. A. (2010). Activation of akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in anopheles stephensi mosquitoes. PLoS Pathogens, 6(7), 1-10. [e1001003]. https://doi.org/10.1371/journal.ppat.1001003

Activation of akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in anopheles stephensi mosquitoes. / Corby-Harris, Vanessa; Drexler, Anna; de Jong, Laurel Watkins; Antonova, Yevgeniya; Pakpour, Nazzy; Ziegler, Rolf; Ramberg, Frank; Lewis, Edwin E.; Brown, Jessica M.; Luckhart, Shirley; Riehle, Michael A.

In: PLoS Pathogens, Vol. 6, No. 7, e1001003, 07.2010, p. 1-10.

Research output: Contribution to journalArticle

Corby-Harris, V, Drexler, A, de Jong, LW, Antonova, Y, Pakpour, N, Ziegler, R, Ramberg, F, Lewis, EE, Brown, JM, Luckhart, S & Riehle, MA 2010, 'Activation of akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in anopheles stephensi mosquitoes', PLoS Pathogens, vol. 6, no. 7, e1001003, pp. 1-10. https://doi.org/10.1371/journal.ppat.1001003
Corby-Harris, Vanessa ; Drexler, Anna ; de Jong, Laurel Watkins ; Antonova, Yevgeniya ; Pakpour, Nazzy ; Ziegler, Rolf ; Ramberg, Frank ; Lewis, Edwin E. ; Brown, Jessica M. ; Luckhart, Shirley ; Riehle, Michael A. / Activation of akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in anopheles stephensi mosquitoes. In: PLoS Pathogens. 2010 ; Vol. 6, No. 7. pp. 1-10.
@article{c9ebb7e509ee4992bb15d066b1b4f658,
title = "Activation of akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in anopheles stephensi mosquitoes",
abstract = "Malaria (Plasmodium spp.) kills nearly one million people annually and this number will likely increase as drug and insecticide resistance reduces the effectiveness of current control strategies. The most important human malaria parasite, Plasmodium falciparum, undergoes a complex developmental cycle in the mosquito that takes approximately two weeks and begins with the invasion of the mosquito midgut. Here, we demonstrate that increased Akt signaling in the mosquito midgut disrupts parasite development and concurrently reduces the duration that mosquitoes are infective to humans. Specifically, we found that increased Akt signaling in the midgut of heterozygous Anopheles stephensi reduced the number of infected mosquitoes by 60-99{\%}. Of those mosquitoes that were infected, we observed a 75-99{\%} reduction in parasite load. In homozygous mosquitoes with increased Akt signaling parasite infection was completely blocked. The increase in midgut-specific Akt signaling also led to an 18-20{\%} reduction in the average mosquito lifespan. Thus, activation of Akt signaling reduced the number of infected mosquitoes, the number of malaria parasites per infected mosquito, and the duration of mosquito infectivity.",
author = "Vanessa Corby-Harris and Anna Drexler and {de Jong}, {Laurel Watkins} and Yevgeniya Antonova and Nazzy Pakpour and Rolf Ziegler and Frank Ramberg and Lewis, {Edwin E.} and Brown, {Jessica M.} and Shirley Luckhart and Riehle, {Michael A.}",
year = "2010",
month = "7",
doi = "10.1371/journal.ppat.1001003",
language = "English (US)",
volume = "6",
pages = "1--10",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - Activation of akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in anopheles stephensi mosquitoes

AU - Corby-Harris, Vanessa

AU - Drexler, Anna

AU - de Jong, Laurel Watkins

AU - Antonova, Yevgeniya

AU - Pakpour, Nazzy

AU - Ziegler, Rolf

AU - Ramberg, Frank

AU - Lewis, Edwin E.

AU - Brown, Jessica M.

AU - Luckhart, Shirley

AU - Riehle, Michael A.

PY - 2010/7

Y1 - 2010/7

N2 - Malaria (Plasmodium spp.) kills nearly one million people annually and this number will likely increase as drug and insecticide resistance reduces the effectiveness of current control strategies. The most important human malaria parasite, Plasmodium falciparum, undergoes a complex developmental cycle in the mosquito that takes approximately two weeks and begins with the invasion of the mosquito midgut. Here, we demonstrate that increased Akt signaling in the mosquito midgut disrupts parasite development and concurrently reduces the duration that mosquitoes are infective to humans. Specifically, we found that increased Akt signaling in the midgut of heterozygous Anopheles stephensi reduced the number of infected mosquitoes by 60-99%. Of those mosquitoes that were infected, we observed a 75-99% reduction in parasite load. In homozygous mosquitoes with increased Akt signaling parasite infection was completely blocked. The increase in midgut-specific Akt signaling also led to an 18-20% reduction in the average mosquito lifespan. Thus, activation of Akt signaling reduced the number of infected mosquitoes, the number of malaria parasites per infected mosquito, and the duration of mosquito infectivity.

AB - Malaria (Plasmodium spp.) kills nearly one million people annually and this number will likely increase as drug and insecticide resistance reduces the effectiveness of current control strategies. The most important human malaria parasite, Plasmodium falciparum, undergoes a complex developmental cycle in the mosquito that takes approximately two weeks and begins with the invasion of the mosquito midgut. Here, we demonstrate that increased Akt signaling in the mosquito midgut disrupts parasite development and concurrently reduces the duration that mosquitoes are infective to humans. Specifically, we found that increased Akt signaling in the midgut of heterozygous Anopheles stephensi reduced the number of infected mosquitoes by 60-99%. Of those mosquitoes that were infected, we observed a 75-99% reduction in parasite load. In homozygous mosquitoes with increased Akt signaling parasite infection was completely blocked. The increase in midgut-specific Akt signaling also led to an 18-20% reduction in the average mosquito lifespan. Thus, activation of Akt signaling reduced the number of infected mosquitoes, the number of malaria parasites per infected mosquito, and the duration of mosquito infectivity.

UR - http://www.scopus.com/inward/record.url?scp=77957686131&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957686131&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1001003

DO - 10.1371/journal.ppat.1001003

M3 - Article

C2 - 20664791

AN - SCOPUS:77957686131

VL - 6

SP - 1

EP - 10

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 7

M1 - e1001003

ER -