The α-proteobacteriumWolbachiais probably the most prevalent, vertically transmitted symbiont on Earth. In contrast with its wide distribution in arthropods,Wolbachiais restricted to one family of animal-parasitic nematodes, the Onchocercidae. This includes filarial pathogens such asOnchocerca volvulus, the cause of human onchocerciasis, or river blindness. The symbiosis between filariae andWolbachiais obligate, although the basis of this dependency is not fully understood. Previous studies suggested thatWolbachiamay provision metabolites (e.g., haem, riboflavin, and nucleotides) and/or contribute to immune defense. Importantly,Wolbachiais restricted to somatic tissues in adult male worms, whereas females also harbor bacteria in the germline. We sought to characterize the nature of the symbiosis betweenWolbachiaandO. ochengi, a bovine parasite representing the closest relative ofO. volvulus. First, we sequenced the complete genome ofWolbachiastrainwOo, which revealed an inability to synthesize riboflavin de novo. Using RNA-seq, we also generated endobacterial transcriptomes from male soma and female germline. In the soma, transcripts for membrane transport and respiration were up-regulated, while the gonad exhibited enrichment for DNA replication and translation. The most abundantWolbachiaproteins, as determined by geLC-MS, included ligands for mammalian Toll-like receptors. Enzymes involved in nucleotide synthesis were dominant among metabolism-related proteins, whereas the haem biosynthetic pathway was poorly represented. We conclude thatWolbachiamay have a mitochondrion-like function in the soma, generating ATP for its host. Moreover, the abundance of immunogenic proteins inwOo suggests a role in diverting the immune system toward an ineffective antibacterial response.

The bacterium Wolbachia (order Rickettsiales) is probably the world's most successful vertically-transmitted symbiont, distributed among a staggering 40% of terrestrial arthropod species. Wolbachia has great potential in vector control due to its ability to manipulate its hosts' reproduction and to impede the replication and dissemination of arboviruses and other pathogens within haematophagous arthropods. In addition, the unexpected presence of Wolbachia in filarial nematodes of medical and veterinary importance has provided an opportunity to target the adult worms of Wuchereria bancrofti, Onchocerca volvulus, and Dirofilaria immitis with safe drugs such as doxycycline. A striking feature of Wolbachia is its phenotypic plasticity between (and sometimes within) hosts, which may be underpinned by its ability to integrate itself into several key processes within eukaryotic cells: oxidative stress, autophagy, and apoptosis. Importantly, despite significant differences in the genomes of arthropod and filarial Wolbachia strains, these nexuses appear to lie on a continuum in different hosts. Here, we consider how iron metabolism may represent a fundamental aspect of host homeostasis that is impacted by Wolbachia infection, connecting disparate pathways ranging from the provision of haem and ATP to programmed cell death, aging, and the recycling of intracellular resources. Depending on how Wolbachia and host cells interact across networks that depend on iron, the gradient between parasitism and mutualism may shift dynamically in some systems, or alternatively, stabilise on one or the other end of the spectrum.

Tick cell lines are increasingly used in many fields of tick and tick-borne disease research. The Tick Cell Biobank was established in 2009 to facilitate the development and uptake of these unique and valuable resources. As well as serving as a repository for existing and new ixodid and argasid tick cell lines, the Tick Cell Biobank supplies cell lines and training in their maintenance to scientists worldwide and generates novel cultures from tick species not already represented in the collection. Now part of the Institute of Infection and Global Health at the University of Liverpool, the Tick Cell Biobank has embarked on a new phase of activity particularly targeted at research on problems caused by ticks, other arthropods and the diseases they transmit in less-developed, lower- and middle-income countries. We are carrying out genotypic and phenotypic characterisation of selected cell lines derived from tropical tick species. We continue to expand the culture collection, currently comprising 63 cell lines derived from 18 ixodid and argasid tick species and one each from the sand fly Lutzomyia longipalpis and the biting midge Culicoides sonorensis, and are actively engaging with collaborators to obtain starting material for primary cell cultures from other midge species, mites, tsetse flies and bees. Outposts of the Tick Cell Biobank will be set up in Malaysia, Kenya and Brazil to facilitate uptake and exploitation of cell lines and associated training by scientists in these and neighbouring countries. Thus the Tick Cell Biobank will continue to underpin many areas of global research into biology and control of ticks, other arthropods and vector-borne viral, bacterial and protozoan pathogens.

Trombidid mites have a unique life cycle in which only the larval stage is ectoparasitic. In the superfamily Trombiculoidea (“chiggers”), the larvae feed preferentially on vertebrates, including humans. Species in the genus Leptotrombidium are vectors of a potentially fatal bacterial infection, scrub typhus, that affects 1 million people annually. Moreover, chiggers can cause pruritic dermatitis (trombiculiasis) in humans and domesticated animals. In the Trombidioidea (velvet mites), the larvae feed on other arthropods and are potential biological control agents for agricultural pests. Here, we present the first trombidid mites genomes, obtained both for a chigger, Leptotrombidium deliense, and for a velvet mite, Dinothrombium tinctorium. Sequencing was performed using Illumina technology. A 180 Mb draft assembly for D. tinctorium was generated from two paired-end and one mate-pair library using a single adult specimen. For L. deliense, a lower-coverage draft assembly (117 Mb) was obtained using pooled, engorged larvae with a single paired-end library. Remarkably, both genomes exhibited evidence of ancient lateral gene transfer from soil-derived bacteria or fungi. The transferred genes confer functions that are rare in animals, including terpene and carotenoid synthesis. Thirty-seven allergenic protein families were predicted in the L. deliense genome, of which nine were unique. Preliminary proteomic analyses identified several of these putative allergens in larvae. Trombidid mite genomes appear to be more dynamic than those of other acariform mites. A priority for future research is to determine the biological function of terpene synthesis in this taxon and its potential for exploitation in disease control.

Wolbachia are alpha-proteobacteria symbionts infecting a large range of arthropod species and two different families of nematodes. Interestingly, these endosymbionts are able to induce diverse phenotypes in their hosts: they are reproductive parasites within many arthropods, nutritional mutualists within some insects and obligate mutualists within their filarial nematode hosts. Defining Wolbachia ‘species’ is controversial and so they are commonly classified into 17 different phylogenetic lineages, termed supergroups, named A–F, H–Q and S. However, available genomic data remain limited and not representative of the full Wolbachia diversity; indeed, of the 24 complete genomes and 55 draft genomes of Wolbachia available to date, 84 % belong to supergroups A and B, exclusively composed of Wolbachia from arthropods. For the current study, we took advantage of a recently developed DNA-enrichment method to produce four complete genomes and two draft genomes of Wolbachia from filarial nematodes. Two complete genomes, wCtub and wDcau, are the smallest Wolbachia genomes sequenced to date (863 988 bp and 863 427 bp, respectively), as well as the first genomes representing supergroup J. These genomes confirm the validity of this supergroup, a controversial clade due to weaknesses of the multilocus sequence typing approach. We also produced the first draft Wolbachia genome from a supergroup F filarial nematode representative (wMhie), two genomes from supergroup D (wLsig and wLbra) and the complete genome of wDimm from supergroup C. Our new data confirm the paradigm of smaller Wolbachia genomes from filarial nematodes containing low levels of transposable elements and the absence of intact bacteriophage sequences, unlike many Wolbachia from arthropods, where both are more abundant. However, we observe differences among the Wolbachia genomes from filarial nematodes: no global co-evolutionary pattern, strong synteny between supergroup C and supergroup J Wolbachia, and more transposable elements observed in supergroup D Wolbachia compared to the other supergroups. Metabolic pathway analysis indicates several highly conserved pathways (haem and nucleotide biosynthesis, for example) as opposed to more variable pathways, such as vitamin B biosynthesis, which might be specific to certain host–symbiont associations. Overall, there appears to be no single Wolbachia –filarial nematode pattern of co-evolution or symbiotic relationship.

Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus. Therefore, elimination programs need time frames of decades, well exceeding the life span of adult worms. The situation is worsened by decreased ivermectin efficacy after long-term therapy. To improve treatment options against onchocerciasis, a drug development candidate should ideally kill or irreversibly sterilize adult worms. Emodepside is a broad-spectrum anthelmintic used for the treatment of parasitic nematodes in cats and dogs (Profender and Procox). Our current knowledge of the pharmacology of emodepside is the result of more than 2 decades of intensive collaborative research between academia and the pharmaceutical industry. Emodepside has a novel mode of action with a broad spectrum of activity, including against extraintestinal nematode stages such as migrating larvae or macrofilariae. Therefore, emodepside is considered to be among the most promising candidates for evaluation as an adulticide treatment against onchocerciasis. Consequently, in 2014, Bayer and the Drugs for Neglected Diseases initiative (DNDi) started a collaboration to develop emodepside for the treatment of patients suffering from the disease. Macrofilaricidal activity has been demonstrated in various models, including Onchocerca ochengi in cattle, the parasite most closely related to O. volvulus. Emodepside has now successfully passed Phase I clinical trials, and a Phase II study is planned. This Bayer–DNDi partnership is an outstanding example of “One World Health,” in which experience gained in veterinary science and drug development is translated to human health and leads to improved tools to combat neglected tropical diseases (NTDs) and shorten development pathways and timelines in an otherwise neglected area.