This Article Full Text (PDF) Other Versions of this Article: MCB.00553-08v1 28/20/6196    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Mikolajczak, S. A. Articles by Kappe, S. H.I. PubMed PubMed Citation Articles by Mikolajczak, S. A. Articles by Kappe, S. H.I.

 Previous Article  |  Next Article 

Mol. Cell. Biol. doi:10.1128/MCB.00553-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Distinct malaria parasite sporozoites reveal transcriptional changes that cause differential tissue infection competence in the mosquito vector and mammalian host

Seattle Biomedical Research Institute, Seattle, WA 98109, USA; Division of Molecular Parasitology, Department of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Walter Reed Army Institute for Research, Silver Spring, MD, 20910, USA; Department of Global Health, University of Washington, Seattle, WA, 98195, USA

^* To whom correspondence should be addressed. Email: Stefan.kappe{at}sbri.org.

	Abstract

The malaria parasite sporozoite transmission stage develops and differentiates within parasite oocysts in the Anopheles mosquito midgut. Successful inoculation of the parasite into a mammalian host is critically dependent on the sporozoites ability to first infect the mosquito salivary glands. Remarkable changes in the tissue infection competence are observed as the sporozoites transit from the midgut oocysts to the salivary glands. Our microarray analysis shows that when compared to oocyst sporozoites, salivary gland sporozoites up-regulate expression of at least 124 unique genes. Conversely, oocyst sporozoites show up-regulation of at least 47 genes, (up-regulated in oocyst sporozoites, UOS genes) before they infect the salivary glands. Targeted gene deletion of UOS3, encoding a putative transmembrane protein that localizes to the sporozoite secretory organelles rendered oocyst sporozoites unable to infect the mosquito salivary glands but maintained the parasites liver infection competence. This phenotype demonstrates the significance of differential UOS expression. Thus, the UIS-UOS gene classification provides a framework to elucidate infectivity and transmission success of Plasmodium sporozoites on a whole genome scale. Genes identified herein might represent targets for vector-based transmission blocking strategies (UOS) as well as strategies that prevent mammalian host infection (UIS).