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

نویسندگان

  • Sasisekhar Bennuru
  • James A. Cotton
  • Jose M. C. Ribeiro
  • Alexandra Grote
  • Bhavana Harsha
  • Nancy Holroyd
  • Amruta Mhashilkar
  • Douglas M. Molina
  • Arlo Z. Randall
  • Adam D. Shandling
  • Thomas R. Unnasch
  • Elodie Ghedin
  • Matthew Berriman
  • Sara Lustigman
  • Thomas B. Nutman
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Stage-specific Proteomes from Onchocerca ochengi, Sister Species of the Human River Blindness Parasite, Uncover Adaptations to a Nodular Lifestyle*

Despite 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The etiological agent, Onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. The challenges of obtaining sufficient material have prevente...

متن کامل

A worm's best friend: recruitment of neutrophils by Wolbachia confounds eosinophil degranulation against the filarial nematode Onchocerca ochengi

Onchocerca ochengi, a filarial parasite of cattle, represents the closest relative of the human pathogen, Onchocerca volvulus. Both species harbour Wolbachia endosymbionts and are remarkable in that adult female worms remain viable but sessile for many years while surrounded by host cells and antibodies. The basis of the symbiosis between filariae and Wolbachia is thought to be metabolic, altho...

متن کامل

Lipid profiling of the filarial nematodes Onchocerca volvulus, Onchocerca ochengi and Litomosoides sigmodontis reveals the accumulation of nematode-specific ether phospholipids in the host

Onchocerciasis, a neglected tropical disease prevalent in western and central Africa, is a major health problem and has been targeted for elimination. The causative agent for this disease is the human parasite Onchocerca volvulus. Onchocerca ochengi and Litomosoides sigmodontis, infectious agents of cattle and rodents, respectively, serve as model organisms to study filarial nematode infections...

متن کامل

Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro

The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll-like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane-associated diacylated lipoproteins, was functionally defined in murine mod...

متن کامل

Molecular cloning of adenylate kinase from the human filarial parasite Onchocerca volvulus

Adenylate kinases (ADK) are ubiquitous enzymes that contribute to the homeostasis of adeninenucleotides in living cells. In this study, the cloning of a cDNA encoding an adenylate kinase from the filariaOnchocerca volvulus has been described. Using PCR technique, a 281 bp cDNA fragment encoding part ofan adenylate kinase was isolated from an O. volvulus cDNA library. Use of this fragment as a p...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016