The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection

PLoS Pathogens

John Adams¹  Bharath Balu¹  Andy Waters²  Chris Janse²  Jai Ramesar²  Taco Kooij²  Christiaan van Ooij³  N. Luisa Hiller³  Pamela Tamez³  Kasturi Haldar³  Travis Harrison³  Konstantinos Liolios³  Souvik Bhattacharjee³ 

[1] Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America;Department of Parasitology, Malaria Group, Leiden University Medical Center, Leiden, The Netherlands;Department of Pathology, Northwestern University, Chicago, Illinois, United States of America

关键词: Red blood cells;    Plasmodium;    Parasitic diseases;    Sequence motif analysis;    Membrane proteins;    Plasmodium falciparum;    Malarial parasites;    Vesicles;   

DOI  :  10.1371/journal.ppat.1000084

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The malaria agent Plasmodium falciparum is predicted to export a “secretome” of several hundred proteins to remodel the host erythrocyte. Prediction of protein export is based on the presence of an ER-type signal sequence and a downstream Host-Targeting (HT) motif (which is similar to, but distinct from, the closely related Plasmodium Export Element [PEXEL]). Previous attempts to determine the entire secretome, using either the HT-motif or the PEXEL, have yielded large sets of proteins, which have not been comprehensively tested. We present here an expanded secretome that is optimized for both P. falciparum signal sequences and the HT-motif. From the most conservative of these three secretome predictions, we identify 11 proteins that are preserved across human- and rodent-infecting Plasmodium species. The conservation of these proteins likely indicates that they perform important functions in the interaction with and remodeling of the host erythrocyte important for all Plasmodium parasites. Using the piggyBac transposition system, we validate their export and find a positive prediction rate of ∼70%. Even for proteins identified by all secretomes, the positive prediction rate is not likely to exceed ∼75%. Attempted deletions of the genes encoding the conserved exported proteins were not successful, but additional functional analyses revealed the first conserved secretome function. This gave new insight into mechanisms for the assembly of the parasite-induced tubovesicular network needed for import of nutrients into the infected erythrocyte. Thus, genomic screens combined with functional assays provide unexpected and fundamental insights into host remodeling by this major human pathogen.

【 授权许可】

CC BY