Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont

被引:35
作者
Bennuru, Sasisekhar [1 ]
Cotton, James A. [2 ]
Ribeiro, Jose M. C. [3 ]
Grote, Alexandra [4 ]
Harsha, Bhavana [2 ]
Holroyd, Nancy [2 ]
Mhashilkar, Amruta [5 ]
Molina, Douglas M. [6 ]
Randall, Arlo Z. [6 ]
Shandling, Adam D. [6 ]
Unnasch, Thomas R. [5 ]
Ghedin, Elodie [4 ,7 ]
Berriman, Matthew [2 ]
Lustigman, Sara [8 ]
Nutman, Thomas B. [1 ]
机构
[1] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA
[2] Wellcome Trust Sanger Inst, Wellcome Genome Campus, Hinxton, Cambs, England
[3] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA
[4] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA
[5] Univ S Florida, Tampa, FL USA
[6] Antigen Discovery Inc, Irvine, CA USA
[7] NYU, Coll Global Publ Hlth, New York, NY USA
[8] New York Blood Ctr, New York, NY 10021 USA
基金
英国惠康基金; 比尔及梅琳达.盖茨基金会;
关键词
GENE-EXPRESSION; BRUGIA-MALAYI; CATHEPSIN-L; NEMATODE; IMMUNITY; DISEASE; LARVAL; IDENTIFICATION; TETRACYCLINE; PROTEASES;
D O I
10.1128/mBio.02028-16
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, requires additional tools, including drugs, vaccines, and biomarkers of infection. Here, we describe the transcriptome and proteome profiles of the major vector and the human host stages (L1, L2, L3, molting L3, L4, adult male, and adult female) of Onchocerca volvulus along with the proteome of each parasitic stage and of its Wolbachia endosymbiont (wOv). In so doing, we have identified stage-specific pathways important to the parasite's adaptation to its human host during its early development. Further, we generated a protein array that, when screened with well-characterized human samples, identified novel diagnostic biomarkers of O. volvulus infection and new potential vaccine candidates. This immunomic approach not only demonstrates the power of this postgenomic discovery platform but also provides additional tools for onchocerciasis control programs. IMPORTANCE The global onchocerciasis (river blindness) elimination program will have to rely on the development of new tools (drugs, vaccines, biomarkers) to achieve its goals by 2025. As an adjunct to the completed genomic sequencing of O. volvulus, we used a comprehensive proteomic and transcriptomic profiling strategy to gain a comprehensive understanding of both the vector-derived and human host-derived parasite stages. In so doing, we have identified proteins and pathways that enable novel drug targeting studies and the discovery of novel vaccine candidates, as well as useful biomarkers of active infection.
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页数:11
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