Distinct Roles of Plasmodium Rhomboid 1 in Parasite Development and Malaria Pathogenesis

PLoS Pathogens

Marcelo Jacobs-Lorena¹  Prakash Srinivasan¹  Isabelle Coppens¹ 

[1] Malaria Research Institute and Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America

关键词: Parasitic diseases;    Sporozoites;    Plasmodium;    Salivary gl;    s;    Oocysts;    Merozoites;    Gene disruption;    Malarial parasites;   

DOI  :  10.1371/journal.ppat.1000262

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Invasion of host cells by the malaria parasite involves recognition and interaction with cell-surface receptors. A wide variety of parasite surface proteins participate in this process, most of which are specific to the parasite's particular invasive form. Upon entry, the parasite has to dissociate itself from the host-cell receptors. One mechanism by which it does so is by shedding its surface ligands using specific enzymes. Rhomboid belongs to a family of serine proteases that cleave cell-surface proteins within their transmembrane domains. Here we identify and partially characterize a Plasmodium berghei rhomboid protease (PbROM1) that plays distinct roles during parasite development. PbROM1 localizes to the surface of sporozoites after salivary gland invasion. In blood stage merozoites, PbROM1 localizes to the apical end where proteins involved in invasion are also present. Our genetic analysis suggests that PbROM1 functions in the invasive stages of parasite development. Whereas wild-type P. berghei is lethal to mice, animals infected with PbROM1 null mutants clear the parasites efficiently and develop long-lasting protective immunity. The results indicate that P. berghei Rhomboid 1 plays a nonessential but important role during parasite development and identify rhomboid proteases as potential targets for disease control.

【 授权许可】

CC BY