Pharmaceutical Sciences Faculty Publications

Title

Stage-Specific Proteomic Expression Patterns of the Human Filarial Parasite Brugia Malayi and its Endosymbiont Wolbachia

Document Type

Article

Publication Date

6-7-2011

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

ISSN

1091-6490

Volume

108

Issue

23

First Page

9649

Last Page

9654

DOI

10.1073/pnas.1011481108

PubMed ID

21606368

PubMed Central® ID

PMC3111283

Abstract

Global proteomic analyses of pathogens have thus far been limited to unicellular organisms (e.g., protozoa and bacteria). Proteomic analyses of most eukaryotic pathogens (e.g., helminths) have been restricted to specific organs, specific stages, or secretomes. We report here a large-scale proteomic characterization of almost all the major mammalian stages of Brugia malayi, a causative agent of lymphatic filariasis, resulting in the identification of more than 62% of the products predicted from the Bm draft genome. The analysis also yielded much of the proteome of Wolbachia, the obligate endosymbiont of Bm that also expressed proteins in a stage-specific manner. Of the 11,610 predicted Bm gene products, 7,103 were definitively identified from adult male, adult female, blood-borne and uterine microfilariae, and infective L3 larvae. Among the 4,956 gene products (42.5%) inferred from the genome as "hypothetical," the present study was able to confirm 2,336 (47.1%) as bona fide proteins. Analysis of protein families and domains coupled with stage-specific expression highlight the important pathways that benefit the parasite during its development in the host. Gene set enrichment analysis identified extracellular matrix proteins and those with immunologic effects as enriched in the microfilarial and L3 stages. Parasite sex- and stage-specific protein expression identified those pathways related to parasite differentiation and demonstrates stage-specific expression by the Bm endosymbiont Wolbachia as well.

Keywords

Bacterial proteins, brugia malayi, chromatography, liquid, host-pathogen interactions, proteome, proteomics, symbiosis, tandem mass spectrometry, wolbachia

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