Variation in susceptibility of African Plasmodium falciparum malaria parasites to TEP1 mediated killing in Anopheles gambiae mosquitoes.

Maarten Eldering,Rianne Siebelink-Stoter,Isabelle Morlais,Will Roeffen,Robert W Sauerwein,Marga Van De Vegte-Bolmer,Luc Abate,Wouter Graumans,Geert-Jan Van Gemert,Elena A Levashina,Martijn Vos,Teun Bousema

doi:10.1038/srep20440

Abstract

Anopheles gambiae s.s. mosquitoes are efficient vectors for Plasmodium falciparum, although variation exists in their susceptibility to infection. This variation depends partly on the thioester-containing protein 1 (TEP1) and TEP depletion results in significantly elevated numbers of oocysts in susceptible and resistant mosquitoes. Polymorphism in the Plasmodium gene coding for the surface protein Pfs47 modulates resistance of some parasite laboratory strains to TEP1-mediated killing. Here, we examined resistance of P. falciparum isolates of African origin (NF54, NF165 and NF166) to TEP1-mediated killing in a susceptible Ngousso and a refractory L3–5 strain of A. gambiae. All parasite clones successfully developed in susceptible mosquitoes with limited evidence for an impact of TEP1 on transmission efficiency. In contrast, NF166 and NF165 oocyst densities were strongly reduced in refractory mosquitoes and TEP1 silencing significantly increased oocyst densities. Our results reveal differences between African P. falciparum strains in their capacity to evade TEP1-mediated killing in resistant mosquitoes. There was no significant correlation between Pfs47 genotype and resistance of a given P. falciparum isolate for TEP1 killing. These data suggest that polymorphisms in this locus are not the sole mediators of immune evasion of African malaria parasites.

Highlights

Anopheles gambiae s.s. mosquitoes are efficient vectors for Plasmodium falciparum, variation exists in their susceptibility to infection
Two experiments with P. berghei infected mice confirmed that thioester-containing protein 1 (TEP1) silencing was efficient as it caused a significant increase in oocyst numbers in the Double-stranded RNAs were synthesized from plasmids pLL17 (dsTEP1) as compared to dsLacZ mosquitoes (Fig. S2)
It has been suggested that the high disease burden in Africa may be attributed to the parasite adaptation of African P. falciparum strains to their sympatric vector through evasion of TEP1-mediated killing[25]

Summary

Introduction

Anopheles gambiae s.s. mosquitoes are efficient vectors for Plasmodium falciparum, variation exists in their susceptibility to infection This variation depends partly on the thioester-containing protein 1 (TEP1) and TEP depletion results in significantly elevated numbers of oocysts in susceptible and resistant mosquitoes. Polymorphism in the Plasmodium gene coding for the surface protein Pfs[47] modulates resistance of some parasite laboratory strains to TEP1-mediated killing. We examined resistance of P. falciparum isolates of African origin (NF54, NF165 and NF166) to TEP1-mediated killing in a susceptible Ngousso and a refractory L3–5 strain of A. gambiae. There was no significant correlation between Pfs[47] genotype and resistance of a given P. falciparum isolate for TEP1 killing These data suggest that polymorphisms in this locus are not the sole mediators of immune evasion of African malaria parasites. Depending on the parasite genetic composition, TEP1 mediates P. falciparum ookinete killing in A. gambiae mosquitoes[7]

Methods

Results

Conclusion