The genome of the heartworm, Dirofilaria immitis , reveals drug and vaccine targets

Abstract

The heartworm Dirofilaria immitis is an important parasite of dogs. Transmitted by mosquitoes in warmer climatic zones, it is spreading across southern Europe and the Americas at an alarming pace. There is no vaccine, and chemotherapy is prone to complications. To learn more about this parasite, we have sequenced the genomes of D. immitis and its endosymbiont Wolbachia. We predict 10,179 protein coding genes in the 84.2 Mb of the nuclear genome, and 823 genes in the 0.9-Mb Wolbachia genome. The D. immitis genome harbors neither DNA transposons nor active retrotransposons, and there is very little genetic variation between two sequenced isolates from Europe and the United States. The differential presence of anabolic pathways such as heme and nucleotide biosynthesis hints at the intricate metabolic interrelationship between the heartworm and Wolbachia. Comparing the proteome of D. immitis with other nematodes and with mammalian hosts, we identify families of potential drug targets, immune modulators, and vaccine candidates. This genome sequence will support the development of new tools against dirofilariasis and aid efforts to combat related human pathogens, the causative agents of lymphatic filariasis and river blindness.—Godel, C., Kumar, S., Koutsovoulos, G., Ludin, P., Nilsson, D., Comandatore, F., Wrobel, N., Thompson, M., Schmid, C. D., Goto, S., Bringaud, F., Wolstenholme, A., Bandi, C., Epe, C., Kaminsky, R., Blaxter, M., Mäser, P. The genome of the heartworm, Dirofilaria immitis, reveals drug and vaccine targets.

Improved structural annotation of protein-coding genes in theMeloidogyne haplagenome using RNA-Seq

“…e.g. [2][3][4][5] Included in this list are those of two root-knot nematodes (RKN), Meloidogyne hapla 2 and Meloidogyne incognita. 3 Meloidogyne is a large genus of plant parasites that are distributed worldwide and cause substantial loss to agricultural production.…”

Intraspecific Genetic Variation and Phylogenetic Analysis of Dirofilaria immitis Samples from Western China Using Complete ND1 and 16S rDNA Gene Sequences

“…Recent breakthroughs have been reported for research on the D. immitis transcriptome, 11 secretome, 12 nuclear genome, 13 and microRNAs. 14 Mitochondrial DNA (mtDNA) sequencing has been used for identification of filariae and for investigating genetic variability and phylogenetic relationships; however, these studies were limited to mitochondrial DNA gene partial fragment analysis.…”

Comparative Analysis of the Secretome from a Model Filarial Nematode (Litomosoides sigmodontis) Reveals Maximal Diversity in Gravid Female Parasites

“…Moreover, many filarial species carry obligate bacterial endosymbionts (Wolbachia), which may also stimulate the immune response during infection (8). As part of global efforts to improve prevention and treatment of these diseases, large-scale projects have been undertaken, including sequencing of the nematodes (9 -11) and their Wolbachia (10,12,13), and proteomic analyses of both whole organisms and excretory-secretory products (ESP) (14,15). Additionally, two studies (both on B. malayi) have examined lifecycle stage-specific secretomes (16,17).…”