Spatial transcriptomics reveals antiparasitic targets associated with essential behaviors in the human parasite Brugia malayi

Lymphatic filariasis (LF) is a chronic debilitating neglected tropical disease (NTD) caused by mosquito-transmitted nematodes that afflicts over 60 million people. Control of LF relies on routine mass drug administration with antiparasitics that clear circulating larval parasites but are ineffective against adults. The development of effective adulticides is hampered by a poor understanding of the processes and tissues driving parasite survival in the host. The adult filariae head region contains essential tissues that control parasite feeding, sensory, secretory, and reproductive behaviors, which express promising molecular substrates for the development of antifilarial drugs, vaccines, and diagnostics. We have adapted spatial transcriptomic approaches to map gene expression patterns across these prioritized but historically intractable head tissues. Spatial and tissue-resolved data reveal distinct biases in the origins of known drug targets and secreted antigens. These data were used to identify potential new drug and vaccine targets, including putative hidden antigens expressed in the alimentary canal, and to spatially associate receptor subunits belonging to druggable families. Spatial transcriptomic approaches provide a powerful resource to aid gene function inference and seed antiparasitic discovery pipelines across helminths of relevance to human and animal health.

Parasite–offspring competition for female resources can explain male-biased parasitism in plants

Male-biased susceptibility to parasites is common in dioecious plants. However, why males have higher parasite loads than females is unclear. Unlike males, females must subsidize post-fertilization costs of reproduction (e.g. seed and fruit development). As a result, females may have smaller pools of resources potentially available to parasites, thus leading to lower parasite loads. We tested this prediction in New Zealand's largest native moth (Aenetus virescens: Lepidoptera), whose larvae parasitizeAristotelia serrata(Elaeocarpaceae), an endemic species of dioecious tree. We measured parasite loads in male and female trees, as well as annual seed set in females. We then derived a technique to equate the energetic cost of seed set in females to an equivalent number of parasitic larvae. Our results showed evidence for male-biased parasitism: male trees harboured more larval parasites than female trees. However, when parasite loads in males were compared with parasite loads in females, plus the energetic cost of seed production calculated as an equivalent number of parasitic larvae, differences in parasitism between the sexes disappeared. We conclude that male-biased parasitism in plants could arise from parasite–offspring (i.e. herbivore–seed) competition for female resources.

Spatial variability of larval parasites harboured by two crab species in an estuarine environment in Argentina

Soft bottom intertidals of the Atlantic SW are dominated by the semi-terrestrial crabNeohelice granulataand the grapsid crabCyrtograpsus angulatus. They are similar in size butC. angulatusis mainly a subtidal species, whileN. granulatainhabits the intertidal zones, thus the two species overlap only during high tides in this area. Since these distribution differences between crab species across the Mar Chiquita Coastal lagoon may affect digenean infection success, the objective of this work is to describe the spatial differences in parasite infection levels and their selectivity on the host. To determine possible spatial differences in parasitism levels between sites and crab species across the lagoon, three areas dominated byN. granulatawere selected and adult crabs ofN. granulataandC. angulatuswere collected. Both crab species harboured metacercariae of the digeneansMicrophallus szidatiandMaritrema bonaerensis(Microphallidae), and cystacanths of the acanthocephalanProfilicollis chasmagnathi(Profilicollidae). Digenean species showed preferences between the two crabs.Maritrema bonaerensismean intensity was higher inN. granulatathan inC. angulatus, while the opposite trend was found forM. szidatiand could indicate some level of specificity. These results, nevertheless, depended on the study site. ForP. chasmagnathithe highest values of mean intensity depended more on the site than on the crab species. The values found here, compared with previous works from both crab species, suggest that besides the spatial heterogeneity, interspecific competition between parasites could explain the differences observed.

Parasite infracommunities of a specialized marine fish species in a compound community dominated by generalist parasites

The structure and composition of parasite communities of Mullus argentinae were analysed under two alternative hypotheses in a sample of 75 specimens caught off Mar del Plata, Argentina (38°27′S, 57°90′W). The first, based on the dominance of trophically transmitted larval parasites of low host-specificity among fish species in the region, predicts that infracommunities will be random subsets of regionally available species. The second, based on previous studies on other mullids, predicts that infracommunities will be dominated by adult digeneans. The parasite fauna of goatfishes was mainly composed of endoparasites, with metacercariae of Prosorhynchus australis accounting for most individual parasites and greatly affecting infracommunity descriptors. Its importance was reinforced by the low number of trophically transmitted larval parasites. Both hypotheses were refuted; parasite communities were not dominated either by trophically transmitted larval parasites of low host-specificity or by adult digeneans. Prosorhynchus australis was the only species displaying any degree of phylogenetic specificity. Therefore, the influence of phylogenetic factors seems to exceed that of ecological ones in determining the observed structure of infracommunities. However, it is precisely host ecology that allows P. australis to become the determinant of infracommunity structure by constraining the acquisition of other parasites. Studies aiming to determine the relative importance of evolutionary and ecological processes as structuring forces of parasite communities should take into account not only the identity and specificity of their component parasites, but also their availability in the compound community.

Parasite fauna of the mediterranean grenadier Coryphaenoides mediterraneus (Giglioli, 1893) from the Mid-Atlantic Ridge (MAR)

A total of 38 Coryphaenoides mediterraneus from the Charlie-Gibbs Fracture Zone (CGFZ), a part of the Mid-Atlantic Ridge (MAR), was studied for parasites and feeding ecology. Sixteen different parasite species were found, most of them belonging to the Digenea (6 species) and Nematoda (6). Twelve new host and 11 new locality records were established, and 8 deep-sea generalists and 5 deep-sea specialists were found. Twelve adult and 3 larval parasites occurred, with Allopodocotyle margolisi (Digenea), Tetraphyllidea indet. (Scolex pleuronectis, Cestoda) and Ascarophis longiovata (Nematoda) being the predominant species. These parasites reached a prevalence of 50.0%, 86.8% and 68.4% with an intensity of infection of 1–10, 1–91 and 1–74, respectively. The food consisted of crustaceans and cephalopods; no further prey items such as fish could be identified. Coryphaenoides mediterraneus demonstrates a parasite fauna similar to that of other deep-sea macrourids. No MAR-specific parasite species were found, and the collected helminths are common fish parasites of the North Atlantic deep-sea basin and the adjacent continental shelf regions. Only few larval epipelagic generalists such as ascaridoid nematodes were found, due to the deep origin of the studied fish between 1700–3500 m. The recorded species rich parasite fauna reflects the wide depth range and opportunistic feeding behaviour of C. mediterraneus on benthopelagic food. The recorded parasite species composition around the MAR appears to be similar to other deep-sea locations in the Atlantic Ocean, demonstrating the wide zoogeographical distribution of these deep-sea metazoans. Consequences of the MAR, the CGFZ and the homogeneous deep-sea environmental conditions for the parasite species distribution are discussed.

Pathogenicity of the hymenolepidid cestode Microsomacanthus hopkinsi in its intermediate host, Hyalella azteca: implications for transmission, host fitness, and host populations

Infection by larval parasites can have severe consequences on intermediate hosts that affect transmission, fecundity and fitness of the host, and host population structure. This study examines the pathogenic effects of cysticercoid larvae of the hymenolepidid cestode Microsomacanthus hopkinsi (Schiller, 1951) on its amphipod intermediate host, Hyalella azteca Saussure, 1858. There was a significant, positive relationship between oncosphere consumption, cysticercoid burden, and age in short-term experiments in which groups of H. azteca were exposed individually to single egg packets of M. hopkinsi during instars 1, 2, 3, 4, 6, 8, and 9; however, there was no correlation between oncosphere consumption and the intensity of infection in the amphipod hosts within each instar. The mean number of moults over a 14 day experimental period was significantly less in infected amphipods than in their respective controls. In short-term experiments, the greatest mortality appeared to be limited to amphipods exposed during the earliest instars; little mortality was observed in amphipods exposed during instar 4 or later. Long-term experiments revealed a significant negative effect of infection on the overall life span of both male and female H. azteca exposed individually to a single egg packet during instar 4. Of 72 females infected during instar 4 and provided with mates during instar 6, only 1 and 4 produced broods in instars 8 and 9, respectively, compared with 58 and 57 of 72 control females. Broods produced by infected females were significantly smaller than those of control females. Infected individuals were less likely to mate successfully. The results are discussed in terms of their consequences for transmission, host fitness, and potential effects on host populations.

Spatiotemporal heterogeneity in recruitment of larval parasites to shore crab intermediate hosts: the influence of shorebird definitive hosts

Parasitism is a major biotic determinant of animal population dynamics and community structure. Temporal and spatial heterogeneity in parasitism is commonly observed in intermediate host populations. Understanding the causes of temporal and spatial variation in the recruitment of parasites is crucial if we are to manage host populations and animal communities effectively. Here, the temporal and spatial dynamics of Profilicollis antarcticus and Profilicollis novaezelandensis (Acanthocephala) infections in three species of shore crabs (Macrophthalmus hirtipes, Hemigrapsus edwardsii, and Hemigrapsus crenulatus) are examined in relation to the distribution and abundance of shorebird definitive hosts. Temporal patterns of infection were observed in M. hirtipes but not the other two species. Spatial heterogeneity in recruitment of acanthocephalan larvae to M. hirtipes and H. edwardsii populations was found both within and between locations. Weak evidence is found that infection levels in crab populations are related to the distribution and abundance of shorebird hosts both temporally and spatially. In this system, abiotic factors seem to be at least as important in determining how infection levels vary in time and space as the input of parasite eggs from bird definitive hosts.

Calgranulin C Has Filariacidal and Filariastatic Activity

ABSTRACT The calgranulins are a family of calcium- and zinc-binding proteins produced by neutrophils, monocytes, and other cells. Calgranulins are released during inflammatory responses and have antimicrobial activity. Recently, one of the calgranulins, human calgranulin C (CaGC), has been implicated as an important component of the host responses that limit the parasite burden during filarial nematode infections. The goal of this work was to test the hypothesis that human CaGC has biologic activity against filarial parasites. Brugia malayi microfilariae and adults were exposed in vitro to 0.75 to 100 nM recombinant human CaGC. Recombinant CaGC affected adult and larval parasites in a dose-dependent fashion. Microfilariae were more sensitive to the action of CaGC than were adult parasites. At high levels, CaGC was both macrofilariacidal and microfilariacidal. At lower levels, the percentage of parasites killed was dependent on the level of CaGC in the culture system. The larvae not killed had limited motility. The filariastatic effect of low-level CaGC was reversed when the CaGC was removed from the culture system. Immunohistochemical analysis demonstrated that human CaGC accumulated in the cells of the hypodermis-lateral chord of adult and larval parasites. The antifilarial activity of CaGC was not due to the sequestration of zinc. Thus, the cellular and molecular mechanisms that result in the production and release of CaGC in humans may play a key role in the regulation of filarial parasite numbers.