title: Glucose and Glycogen Metabolism in Brugia malayi Is Associated with Wolbachia Symbiont Fitness.
abstract: Wolbachia are endosymbiotic bacteria found in the majority of arthropods and filarial nematodes of medical and veterinary importance. They have evolved a wide range of symbiotic associations. In filarial nematodes that cause human lymphatic filariasis (Wuchereria bancrofti, Brugia malayi) or onchocerciasis (Onchocerca volvulus), Wolbachia are important for parasite development, reproduction and survival. The symbiotic bacteria rely in part on nutrients and energy sources provided by the host. Genomic analyses suggest that the strain of Wolbachia found in B. malayi (wBm) lacks the genes for two glycolytic enzymes--6-phosphofructokinase and pyruvate kinase--and is thus potentially unable to convert glucose into pyruvate, an important substrate for energy generation. The Wolbachia surface protein, wBm00432, is complexed to six B. malayi glycolytic enzymes, including aldolase. In this study we characterized two B. malayi aldolase isozymes and found that their expression is dependent on Wolbachia fitness and number. We confirmed by immuno-transmission electron microscopy that aldolase is associated with the Wolbachia surface. RNAi experiments suggested that aldolase-2 plays a significant role in both Wolbachia survival and embryogenesis in B. malayi. Treatment with doxycycline reduced Wolbachia fitness and increased the amount of both glucose and glycogen detected in the filarial parasite, indicating that glucose metabolism and glycogen storage in B. malayi are associated with Wolbachia fitness. This metabolic co-dependency between Wolbachia and its filarial nematode indicates that glycolysis could be a shared metabolic pathway between the bacteria and B. malayi, and thus a potential new target for anti-filarial therapy.
authors.affiliation: Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, United States of America.
authors.forename: Denis
authors.initials: D
authors.lastname: Voronin
authors.affiliation: Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, United States of America.
authors.forename: Saheed
authors.initials: S
authors.lastname: Bachu
authors.affiliation: Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Shlossman
authors.affiliation: Global Health Infectious Disease Research Program, Department of Global Health, College of Public Health, University of South Florida, Tampa, FL 33612, United States of America.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Unnasch
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology, and College of Global Public Health, New York University, New York, NY 10003, United States of America.
authors.forename: Elodie
authors.initials: E
authors.lastname: Ghedin
authors.affiliation: Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, United States of America.
authors.forename: Sara
authors.initials: S
authors.lastname: Lustigman
mesh_terms: D000446:Aldehyde-Lyases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D015153:Blotting, Western; D017178:Brugia malayi / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006019:Glycolysis; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000187:drug effects; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013559:Symbiosis / Q000187:drug effects; D020577:Wolbachia / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015801:Helminth Proteins; D006003:Glycogen; D000446:Aldehyde-Lyases; D005947:Glucose; D004318:Doxycycline