title: Defining Brugia malayi and Wolbachia symbiosis by stage-specific dual RNA-seq.
abstract: Filarial nematodes currently infect up to 54 million people worldwide, with millions more at risk for infection, representing the leading cause of disability in the developing world. Brugia malayi is one of the causative agents of lymphatic filariasis and remains the only human filarial parasite that can be maintained in small laboratory animals. Many filarial nematode species, including B. malayi, carry an obligate endosymbiont, the alpha-proteobacteria Wolbachia, which can be eliminated through antibiotic treatment. Elimination of the endosymbiont interferes with development, reproduction, and survival of the worms within the mamalian host, a clear indicator that the Wolbachia are crucial for survival of the parasite. Little is understood about the mechanism underlying this symbiosis.
  
  
  
  To better understand the molecular interplay between these two organisms we profiled the transcriptomes of B. malayi and Wolbachia by dual RNA-seq across the life cycle of the parasite. This helped identify functional pathways involved in this essential symbiotic relationship provided by the co-expression of nematode and bacterial genes. We have identified significant stage-specific and gender-specific differential expression in Wolbachia during the nematode's development. For example, during female worm development we find that Wolbachia upregulate genes involved in ATP production and purine biosynthesis, as well as genes involved in the oxidative stress response.
  
  
  
  This global transcriptional analysis has highlighted specific pathways to which both Wolbachia and B. malayi contribute concurrently over the life cycle of the parasite, paving the way for the development of novel intervention strategies.
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, New York, United States of America.
authors.forename: Alexandra
authors.identifier: 0000-0002-1887-4190
authors.initials: A
authors.lastname: Grote
authors.affiliation: Molecular Parasitology, New York Blood Center, New York, New York, United States of America.
authors.forename: Denis
authors.initials: D
authors.lastname: Voronin
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, New York, United States of America.
authors.forename: Tao
authors.initials: T
authors.lastname: Ding
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, New York, United States of America.
authors.forename: Alan
authors.initials: A
authors.lastname: Twaddle
authors.affiliation: Department of Global Health, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Unnasch
authors.affiliation: Molecular Parasitology, New York Blood Center, New York, New York, United States of America.
authors.forename: Sara
authors.initials: S
authors.lastname: Lustigman
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, New York, United States of America.|College of Global Public Health, New York University, New York, New York, United States of America.
authors.forename: Elodie
authors.initials: E
authors.lastname: Ghedin
mesh_terms: D000818:Animals; D017178:Brugia malayi / Q000254:growth & development* / Q000382:microbiology*; D005260:Female; D020869:Gene Expression Profiling; D017423:Sequence Analysis, RNA; D013559:Symbiosis; D020577:Wolbachia / Q000502:physiology*