Depletion of the Plasmodium berghei thrombospondin-related sporozoite protein reveals a role in host cell entry by sporozoites.
The malaria parasite sporozoite stage develops in the mosquito vector and is transmitted to the mammalian host by bite. Sporozoites engage in multiple interactions with vector and host tissue on the journey from their oocyst origin to their final destination inside hepatocytes. Several malaria proteins have been identified that mediate sporozoite interactions with target tissues such as secreted and surface-associated ligands CSP and TRAP, which contain a thrombospondin type 1 repeat (TSR). Recently, we identified thrombospondin-related sporozoite protein (TRSP) in Plasmodium sporozoites, which exhibits a single TSR in its putative extracellular N-terminal region and is highly conserved among Plasmodium species. Here, we show using targeted gene disruption in the rodent malaria model Plasmodium berghei, that lack of TRSP has no effect on the asexual blood stage cycle, parasite transmission to the mosquito, sporozoite development and infection of mosquito salivary glands. However, analysis of TRSP knockout sporozoites in vitro and in vivo indicates that this protein has a significant role in hepatocyte entry and therefore liver infection. Thus, TRSP is an additional TSR-containing malaria parasite protein that is mainly involved in initial infection of the mammalian host.
Labaied
Mehdi
M
Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
Camargo
Nelly
N
Kappe
Stefan H I
SH
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D017353:Gene Deletion; D022781:Hepatocytes / Q000469:parasitology; D006801:Humans; D008288:Malaria / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D034101:Sporozoites / Q000378:metabolism / Q000502:physiology*; D019699:Thrombospondins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D015800:Protozoan Proteins; D019699:Thrombospondins