The Transmembrane Isoform of Plasmodium falciparum MAEBL Is Essential for the Invasion of Anopheles Salivary Glands

Fabian E Saenz,Sarita R Mendonca,John H Adams,Jonah Smith,Bharath Balu

doi:10.1371/journal.pone.0002287

Fabian E Saenz, Sarita R Mendonca + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0002287

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Journal: PLoS ONE	Publication Date: May 28, 2008
Citations: 81	License type: CC BY 4.0

Affiliation: University of South Florida, University of Notre Dame

Abstract

Malaria transmission depends on infective stages in the mosquito salivary glands. Plasmodium sporozoites that mature in midgut oocysts must traverse the hemocoel and invade the mosquito salivary glands in a process thought to be mediated by parasite ligands. MAEBL, a homologue of the transmembrane EBP ligands essential in merozoite invasion, is expressed abundantly in midgut sporozoites. Alternative splicing generates different MAEBL isoforms and so it is unclear what form is functionally essential. To identify the MAEBL isoform required for P. falciparum (NF54) sporozoite invasion of salivary glands, we created knockout and allelic replacements each carrying CDS of a single MAEBL isoform. Only the transmembrane form of MAEBL is essential and is the first P. falciparum ligand validated as essential for invasion of Anopheles salivary glands. MAEBL is the first P. falciparum ligand experimentally determined to be essential for this important step in the life cycle where the vector becomes infectious for transmitting sporozoites to people. With an increasing emphasis on advancing vector-based transgenic methods for suppression of malaria, it is important that this type of study, using modern molecular genetic tools, is done with the agent of the human disease. Understanding what P. falciparum sporozoite ligands are critical for mosquito transmission will help validate targets for vector-based transmission-blocking strategies.

Highlights

Plasmodium falciparum is the malaria parasite responsible for several million deaths each year
Three independent maebl knockout clones were created as negative controls and NF54 parental parasites were used as positive controls for invasion of the mosquito salivary glands
In this study we provide the first characterization of a P. falciparum ligand essential for the invasion of the mosquito salivary glands

Summary

Introduction

Plasmodium falciparum is the malaria parasite responsible for several million deaths each year. The sporozoites are released in the hemolymph and relatively few manage to invade the distal and medial lobes of the salivary gland [3]. Invasion of the salivary glands is a two-stage process that requires traversal of the basal lamina and entry into the salivary gland cell [1]. Similar to merozoite invasion of erythrocytes, invasion of salivary glands occurs in several steps: initial attachment, reorientation, junction formation and entry via a moving junction [1]. The sporozoite has organelles, such as the micronemes and the rhoptries, which have proteins to mediate invasion of the host cells [4]

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