Abstract:
:Malaria starts with the infection of the liver of the host by Plasmodium sporozoites, the parasite form transmitted by infected mosquitoes. Sporozoites migrate through several hepatocytes by breaching their plasma membranes before finally infecting one with the formation of an internalization vacuole. Migration through host cells induces apical regulated exocytosis in sporozoites. Here we show that apical regulated exocytosis is induced by increases in cAMP in sporozoites of rodent (P. yoelii and P. berghei) and human (P. falciparum) Plasmodium species. We have generated P. berghei parasites deficient in adenylyl cyclase alpha (ACalpha), a gene containing regions with high homology to adenylyl cyclases. PbACalpha-deficient sporozoites do not exocytose in response to migration through host cells and present more than 50% impaired hepatocyte infectivity in vivo. These effects are specific to ACalpha, as re-introduction of ACalpha in deficient parasites resulted in complete recovery of exocytosis and infection. Our findings indicate that ACalpha and increases in cAMP levels are required for sporozoite apical regulated exocytosis, which is involved in sporozoite infection of hepatocytes.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Ono T,Cabrita-Santos L,Leitao R,Bettiol E,Purcell LA,Diaz-Pulido O,Andrews LB,Tadakuma T,Bhanot P,Mota MM,Rodriguez Adoi
10.1371/journal.ppat.1000008subject
Has Abstractpub_date
2008-02-29 00:00:00pages
e1000008issue
2eissn
1553-7366issn
1553-7374journal_volume
4pub_type
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