The malaria secretome: from algorithms to essential function in blood stage infection.
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-06-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000084&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849687140437327872 |
|---|---|
| author | Christiaan van Ooij Pamela Tamez Souvik Bhattacharjee N Luisa Hiller Travis Harrison Konstantinos Liolios Taco Kooij Jai Ramesar Bharath Balu John Adams Andrew P Waters Chris J Janse Kasturi Haldar |
| author_facet | Christiaan van Ooij Pamela Tamez Souvik Bhattacharjee N Luisa Hiller Travis Harrison Konstantinos Liolios Taco Kooij Jai Ramesar Bharath Balu John Adams Andrew P Waters Chris J Janse Kasturi Haldar |
| author_sort | Christiaan van Ooij |
| collection | DOAJ |
| description | 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 approximately 70%. Even for proteins identified by all secretomes, the positive prediction rate is not likely to exceed approximately 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. |
| format | Article |
| id | doaj-art-e81e08155fee4067a21b131a88253473 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2008-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-e81e08155fee4067a21b131a882534732025-08-20T03:22:26ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742008-06-0146e100008410.1371/journal.ppat.1000084The malaria secretome: from algorithms to essential function in blood stage infection.Christiaan van OoijPamela TamezSouvik BhattacharjeeN Luisa HillerTravis HarrisonKonstantinos LioliosTaco KooijJai RamesarBharath BaluJohn AdamsAndrew P WatersChris J JanseKasturi HaldarThe 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 approximately 70%. Even for proteins identified by all secretomes, the positive prediction rate is not likely to exceed approximately 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000084&type=printable |
| spellingShingle | Christiaan van Ooij Pamela Tamez Souvik Bhattacharjee N Luisa Hiller Travis Harrison Konstantinos Liolios Taco Kooij Jai Ramesar Bharath Balu John Adams Andrew P Waters Chris J Janse Kasturi Haldar The malaria secretome: from algorithms to essential function in blood stage infection. PLoS Pathogens |
| title | The malaria secretome: from algorithms to essential function in blood stage infection. |
| title_full | The malaria secretome: from algorithms to essential function in blood stage infection. |
| title_fullStr | The malaria secretome: from algorithms to essential function in blood stage infection. |
| title_full_unstemmed | The malaria secretome: from algorithms to essential function in blood stage infection. |
| title_short | The malaria secretome: from algorithms to essential function in blood stage infection. |
| title_sort | malaria secretome from algorithms to essential function in blood stage infection |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000084&type=printable |
| work_keys_str_mv | AT christiaanvanooij themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT pamelatamez themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT souvikbhattacharjee themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT nluisahiller themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT travisharrison themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT konstantinosliolios themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT tacokooij themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT jairamesar themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT bharathbalu themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT johnadams themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT andrewpwaters themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT chrisjjanse themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT kasturihaldar themalariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT christiaanvanooij malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT pamelatamez malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT souvikbhattacharjee malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT nluisahiller malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT travisharrison malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT konstantinosliolios malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT tacokooij malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT jairamesar malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT bharathbalu malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT johnadams malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT andrewpwaters malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT chrisjjanse malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection AT kasturihaldar malariasecretomefromalgorithmstoessentialfunctioninbloodstageinfection |