Overexpression of phosphatase and tensin homolog improves fitness and decreases Plasmodium falciparum development in Anopheles stephensi

Eric S. Hauck, Yevgeniya Antonova-Koch, Anna Drexler, Jose Pietri, Nazzy Pakpour, Darin Liu, Jacob Blacutt, Michael A Riehle, Shirley Luckhart

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The insulin/insulin-like growth factor signaling (IIS) cascade is highly conserved and regulates diverse physiological processes such as metabolism, lifespan, reproduction and immunity. Transgenic overexpression of Akt, a critical regulator of IIS, was previously shown to shorten mosquito lifespan and increase resistance to the human malaria parasite Plasmodium falciparum. To further understand how IIS controls mosquito physiology and resistance to malaria parasite infection, we overexpressed an inhibitor of IIS, phosphatase and tensin homolog (PTEN), in the Anopheles stephensi midgut. PTEN overexpression inhibited phosphorylation of the IIS protein FOXO, an expected target for PTEN, in the midgut of A. stephensi. Further, PTEN overexpression extended mosquito lifespan and increased resistance to P. falciparum development. The reduction in parasite development did not appear to be due to alterations in an innate immune response, but rather was associated with increased expression of genes regulating autophagy and stem cell maintenance in the midgut and with enhanced midgut barrier integrity. In light of previous success in genetically targeting the IIS pathway to alter mosquito lifespan and malaria parasite transmission, these data confirm that multiple strategies to genetically manipulate IIS can be leveraged to generate fit, resistant mosquitoes for malaria control.

Original languageEnglish (US)
Pages (from-to)775-787
Number of pages13
JournalMicrobes and Infection
Volume15
Issue number12
DOIs
StatePublished - Nov 2013

Fingerprint

Anopheles
Plasmodium falciparum
Phosphoric Monoester Hydrolases
Culicidae
Mosquito Control
Malaria
Parasites
Physiological Phenomena
Parasitic Diseases
Falciparum Malaria
Autophagy
Somatomedins
Innate Immunity
Reproduction
Immunity
Stem Cells
Maintenance
Phosphorylation
Insulin
Gene Expression

Keywords

  • Anopheles stephensi
  • Insulin/insulin-like growth factor signaling (IIS)
  • Malaria
  • Mosquito
  • Phosphatase and tensin homolog (PTEN)
  • Plasmodium falciparum

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Overexpression of phosphatase and tensin homolog improves fitness and decreases Plasmodium falciparum development in Anopheles stephensi. / Hauck, Eric S.; Antonova-Koch, Yevgeniya; Drexler, Anna; Pietri, Jose; Pakpour, Nazzy; Liu, Darin; Blacutt, Jacob; Riehle, Michael A; Luckhart, Shirley.

In: Microbes and Infection, Vol. 15, No. 12, 11.2013, p. 775-787.

Research output: Contribution to journalArticle

Hauck, Eric S. ; Antonova-Koch, Yevgeniya ; Drexler, Anna ; Pietri, Jose ; Pakpour, Nazzy ; Liu, Darin ; Blacutt, Jacob ; Riehle, Michael A ; Luckhart, Shirley. / Overexpression of phosphatase and tensin homolog improves fitness and decreases Plasmodium falciparum development in Anopheles stephensi. In: Microbes and Infection. 2013 ; Vol. 15, No. 12. pp. 775-787.
@article{135a6b17578d4badb07ba3539221386a,
title = "Overexpression of phosphatase and tensin homolog improves fitness and decreases Plasmodium falciparum development in Anopheles stephensi",
abstract = "The insulin/insulin-like growth factor signaling (IIS) cascade is highly conserved and regulates diverse physiological processes such as metabolism, lifespan, reproduction and immunity. Transgenic overexpression of Akt, a critical regulator of IIS, was previously shown to shorten mosquito lifespan and increase resistance to the human malaria parasite Plasmodium falciparum. To further understand how IIS controls mosquito physiology and resistance to malaria parasite infection, we overexpressed an inhibitor of IIS, phosphatase and tensin homolog (PTEN), in the Anopheles stephensi midgut. PTEN overexpression inhibited phosphorylation of the IIS protein FOXO, an expected target for PTEN, in the midgut of A. stephensi. Further, PTEN overexpression extended mosquito lifespan and increased resistance to P. falciparum development. The reduction in parasite development did not appear to be due to alterations in an innate immune response, but rather was associated with increased expression of genes regulating autophagy and stem cell maintenance in the midgut and with enhanced midgut barrier integrity. In light of previous success in genetically targeting the IIS pathway to alter mosquito lifespan and malaria parasite transmission, these data confirm that multiple strategies to genetically manipulate IIS can be leveraged to generate fit, resistant mosquitoes for malaria control.",
keywords = "Anopheles stephensi, Insulin/insulin-like growth factor signaling (IIS), Malaria, Mosquito, Phosphatase and tensin homolog (PTEN), Plasmodium falciparum",
author = "Hauck, {Eric S.} and Yevgeniya Antonova-Koch and Anna Drexler and Jose Pietri and Nazzy Pakpour and Darin Liu and Jacob Blacutt and Riehle, {Michael A} and Shirley Luckhart",
year = "2013",
month = "11",
doi = "10.1016/j.micinf.2013.05.006",
language = "English (US)",
volume = "15",
pages = "775--787",
journal = "Microbes and Infection",
issn = "1286-4579",
publisher = "Elsevier Masson SAS",
number = "12",

}

TY - JOUR

T1 - Overexpression of phosphatase and tensin homolog improves fitness and decreases Plasmodium falciparum development in Anopheles stephensi

AU - Hauck, Eric S.

AU - Antonova-Koch, Yevgeniya

AU - Drexler, Anna

AU - Pietri, Jose

AU - Pakpour, Nazzy

AU - Liu, Darin

AU - Blacutt, Jacob

AU - Riehle, Michael A

AU - Luckhart, Shirley

PY - 2013/11

Y1 - 2013/11

N2 - The insulin/insulin-like growth factor signaling (IIS) cascade is highly conserved and regulates diverse physiological processes such as metabolism, lifespan, reproduction and immunity. Transgenic overexpression of Akt, a critical regulator of IIS, was previously shown to shorten mosquito lifespan and increase resistance to the human malaria parasite Plasmodium falciparum. To further understand how IIS controls mosquito physiology and resistance to malaria parasite infection, we overexpressed an inhibitor of IIS, phosphatase and tensin homolog (PTEN), in the Anopheles stephensi midgut. PTEN overexpression inhibited phosphorylation of the IIS protein FOXO, an expected target for PTEN, in the midgut of A. stephensi. Further, PTEN overexpression extended mosquito lifespan and increased resistance to P. falciparum development. The reduction in parasite development did not appear to be due to alterations in an innate immune response, but rather was associated with increased expression of genes regulating autophagy and stem cell maintenance in the midgut and with enhanced midgut barrier integrity. In light of previous success in genetically targeting the IIS pathway to alter mosquito lifespan and malaria parasite transmission, these data confirm that multiple strategies to genetically manipulate IIS can be leveraged to generate fit, resistant mosquitoes for malaria control.

AB - The insulin/insulin-like growth factor signaling (IIS) cascade is highly conserved and regulates diverse physiological processes such as metabolism, lifespan, reproduction and immunity. Transgenic overexpression of Akt, a critical regulator of IIS, was previously shown to shorten mosquito lifespan and increase resistance to the human malaria parasite Plasmodium falciparum. To further understand how IIS controls mosquito physiology and resistance to malaria parasite infection, we overexpressed an inhibitor of IIS, phosphatase and tensin homolog (PTEN), in the Anopheles stephensi midgut. PTEN overexpression inhibited phosphorylation of the IIS protein FOXO, an expected target for PTEN, in the midgut of A. stephensi. Further, PTEN overexpression extended mosquito lifespan and increased resistance to P. falciparum development. The reduction in parasite development did not appear to be due to alterations in an innate immune response, but rather was associated with increased expression of genes regulating autophagy and stem cell maintenance in the midgut and with enhanced midgut barrier integrity. In light of previous success in genetically targeting the IIS pathway to alter mosquito lifespan and malaria parasite transmission, these data confirm that multiple strategies to genetically manipulate IIS can be leveraged to generate fit, resistant mosquitoes for malaria control.

KW - Anopheles stephensi

KW - Insulin/insulin-like growth factor signaling (IIS)

KW - Malaria

KW - Mosquito

KW - Phosphatase and tensin homolog (PTEN)

KW - Plasmodium falciparum

UR - http://www.scopus.com/inward/record.url?scp=84884704110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884704110&partnerID=8YFLogxK

U2 - 10.1016/j.micinf.2013.05.006

DO - 10.1016/j.micinf.2013.05.006

M3 - Article

C2 - 23774695

AN - SCOPUS:84884704110

VL - 15

SP - 775

EP - 787

JO - Microbes and Infection

JF - Microbes and Infection

SN - 1286-4579

IS - 12

ER -