The genomes of four tapeworm species reveal adaptations to parasitism.

Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control.

Exposure to the antifouling chemical medetomidine slows development, reduces body mass, and delays metamorphosis in wood frog (Lithobates sylvaticus) tadpoles.

Antifouling chemicals have a long history of causing toxicity to aquatic organisms. We measured growth and developmental timing in wood frog tadpoles exposed to the antifouling chemical medetomidine (10 nM-10 µM) starting at two different developmental stages in static renewal experiments. For tadpoles hatched from egg masses and exposed for 3 weeks to 100 nM and 1 µM, head width/total body length ratio was significantly shorter compared to control. For field-collected tadpoles at Gosner stage 24-25 and exposed for 2 weeks, 1 and 10 µM medetomidine significantly slowed development as measured by Gosner stage. Medetomidine (1 and 10 µM) significantly increased the time to metamorphosis by over 16 days on average, and at 100 nM and 1 µM, it significantly decreased mass at metamorphosis. We discuss the possible effects of antifouling chemicals containing medetomidine on globally threatened groups such as amphibians.

Differential sensitivity to the antifouling chemical medetomidine between wood frog and American toad tadpoles with evidence for low-dose stimulation and high-dose inhibition of metamorphosis.

Antifouling chemicals are legacy contaminants in aquatic ecosystems. Previous experiments have shown that a 14-day exposure to the antifouling chemical medetomidine delays metamorphosis and reduces body mass in wood frog tadpoles. In the present study, we exposed wood frog tadpoles to medetomidine for 3, 7, and 10 days at 100 nM, 1 µM, and 10 µM. We also exposed American toad tadpoles to medetomidine for 3 days at four concentrations (10 nM, 100 nM, 1 µM, and 10 µM) in static renewal experiments. In each experiment, we measured growth, frequency and time to metamorphosis, and mass at metamorphosis. In both species, medetomidine significantly slowed development as measured by the Gosner stage. After 34 days in culture, wood frog tadpoles exposed to 1 and 10 µM medetomidine for as few as 3 days were significantly less developed compared to controls. Toads exposed to 1 µM medetomidine for 3 days were also significantly less developed on day 27, but by day 34, there was no difference from controls. For wood frogs, medetomidine significantly affected time to metamorphosis with a trend for tadpoles at lower concentrations metamorphosing sooner than those at higher concentrations. While medetomidine affected time to metamorphosis in wood frogs, it did not affect fresh mass, dry mass, or mortality compared to controls. Wood frog tadpoles that did not metamorphose after over 90 days in culture were more frequent in high-concentration groups than in the control. In toads, 10 µM medetomidine was 100% lethal within 23 days, but at the same concentration and duration, no wood frog tadpoles died. Lower concentrations were also significantly lethal to toads compared to controls, but tadpoles that survived in 10 and 100 nM metamorphosed sooner than those in 1 µM. Fresh mass of toad tadpoles exposed to 1 µm was significantly smaller at metamorphosis compared to that of controls. Medetomidine also affected the behavior of tadpoles. In toads, medetomidine significantly reduced both percent activity and startle response. In wood frogs, medetomidine significantly reduced percent activity, but increased startle response. We discuss our finding of low-dose stimulation and high-dose inhibition of different life history endpoints in terms of hormetic mechanisms. The differential sensitivity between species in terms of mortality, frequency of metamorphosis, and behavior highlights the potential negative environmental effects of medetomidine to amphibians.

Exposure to SSRI-type antidepressants increases righting time in the marine snail Ilyanassa obsoleta.

Exposure to human antidepressants has been shown to disrupt locomotion and other foot-mediated mechanisms in aquatic snails. We tested the effect of three selective serotonin reuptake inhibitor (SSRI)- and one selective serotonin-norepinephrine reuptake inhibitor (SNRI)-type antidepressants on the righting response in the marine snail, Ilyanassa obsoleta. All four antidepressants (fluoxetine, sertraline, paroxetine, venlafaxine) significantly increased righting time compared with controls with an exposure time as short as 1 h. Dose responses were nonmonotonic with effects seen mainly at the lowest exposure concentrations and shortest duration. The lowest concentration to show an effect was 3.45 µg/L fluoxetine with a 2-h exposure period and is about 3.71 times higher than environmental concentrations. Our results highlight rapid disruption of another foot-mediated behavior in aquatic snails by SSRI-type antidepressants. We discuss these and other reported nonmonotonic dose responses caused by antidepressants in terms of the various possible physiological mechanisms of action in nontarget aquatic species.

The genome of Onchocerca volvulus, agent of river blindness.

Human onchocerciasis is a serious neglected tropical disease caused by the filarial nematode Onchocerca volvulus that can lead to blindness and chronic disability. Control of the disease relies largely on mass administration of a single drug, and the development of new drugs and vaccines depends on a better knowledge of parasite biology. Here, we describe the chromosomes of O. volvulus and its Wolbachia endosymbiont. We provide the highest-quality sequence assembly for any parasitic nematode to date, giving a glimpse into the evolution of filarial parasite chromosomes and proteomes. This resource was used to investigate gene families with key functions that could be potentially exploited as targets for future drugs. Using metabolic reconstruction of the nematode and its endosymbiont, we identified enzymes that are likely to be essential for O. volvulus viability. In addition, we have generated a list of proteins that could be targeted by Federal-Drug-Agency-approved but repurposed drugs, providing starting points for anti-onchocerciasis drug development.