title: Distinct malaria parasite sporozoites reveal transcriptional changes that cause differential tissue infection competence in the mosquito vector and mammalian host.
abstract: The malaria parasite sporozoite transmission stage develops and differentiates within parasite oocysts on the Anopheles mosquito midgut. Successful inoculation of the parasite into a mammalian host is critically dependent on the sporozoite's ability to first infect the mosquito salivary glands. Remarkable changes in tissue infection competence are observed as the sporozoites transit from the midgut oocysts to the salivary glands. Our microarray analysis shows that compared to oocyst sporozoites, salivary gland sporozoites upregulate expression of at least 124 unique genes. Conversely, oocyst sporozoites show upregulation of at least 47 genes (upregulated in oocyst sporozoites [UOS genes]) before they infect the salivary glands. Targeted gene deletion of UOS3, encoding a putative transmembrane protein with a thrombospondin repeat 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 the 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 genes), as well as strategies that prevent mammalian host infection (UIS genes).
authors: Seattle Biomedical Research Institute, Seattle, WA 98109-5219, USA.
authors: Sebastian A
authors: SA
authors: Mikolajczak
authors: Hilda
authors: H
authors: Silva-Rivera
authors: Xinxia
authors: X
authors: Peng
authors: Alice S
authors: AS
authors: Tarun
authors: Nelly
authors: N
authors: Camargo
authors: Vanessa
authors: V
authors: Jacobs-Lorena
authors: Thomas M
authors: TM
authors: Daly
authors: Lawrence W
authors: LW
authors: Bergman
authors: Patricia
authors: P
authors: de la Vega
authors: Jack
authors: J
authors: Williams
authors: Ahmed S I
authors: AS
authors: Aly
authors: Stefan H I
authors: SH
authors: Kappe
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018390:Gene Targeting; D017125:Genes, Protozoan; D006458:Hemolymph / Q000166:cytology / Q000378:metabolism; D006790:Host-Parasite Interactions; D007275:Injections, Intravenous; D007303:Insect Vectors / Q000469:parasitology*; D008288:Malaria / Q000235:genetics* / Q000469:parasitology*; D008322:Mammals / Q000469:parasitology*; D051379:Mice; D033661:Oocysts / Q000166:cytology / Q000378:metabolism; D010271:Parasites / Q000166:cytology / Q000235:genetics / Q000472:pathogenicity; D010963:Plasmodium falciparum / Q000235:genetics; D010967:Plasmodium yoelii / Q000235:genetics; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000469:parasitology; D034101:Sporozoites / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D015800:Protozoan Proteins