The venom of Habrobracon hebetor induces alterations in host metabolism.

The ability of parasitic wasps to manipulate a host's metabolism is under active investigation. Components of venom play a major role in this process. In the present work, we studied the effect of the venom of the ectoparasitic wasp Habrobracon hebetor on the metabolism of the greater wax moth host (Galleria mellonella). We identified and quantified 45 metabolites in the lymph (cell-free hemolymph) of wax moth larvae on the second day after H. hebetor venom injection, using NMR spectroscopy and liquid chromatography coupled with mass spectrometry. These metabolites included 22 amino acids, nine products of lipid metabolism (sugars, amines and alcohols) and four metabolic intermediates related to nitrogenous bases, nucleotides and nucleosides. An analysis of the larvae metabolome suggested that the venom causes suppression of the tricarboxylic acid cycle, an increase in the number of free amino acids in the lymph, an increase in the concentration of trehalose in the lymph simultaneously with a decrease in the amount of glucose, and destructive processes in the fat body tissue. Thus, this parasitoid venom not only immobilizes the prey but also modulates its metabolism, thereby providing optimal conditions for the development of larvae.

Enhancing Reniform Nematode Management in Sweetpotato by Complementing Host-Plant Resistance with Nonfumigant Nematicides.

The reniform nematode (Rotylenchulus reniformis Linford and Oliveira) adversely impacts the quality and quantity of sweetpotato storage roots. Management of R. reniformis in sweetpotato remains a challenge because host plant resistance is not available, fumigants are detrimental to the environment and health, and crop rotation is not effective. We screened a core set of 24 sweetpotato plant introductions (PIs) against R. reniformis. Four PIs were resistant, and 10 were moderately resistant to R. reniformis, suggesting these PIs can serve as sources of resistance for sweetpotato resistance breeding programs. PI 595869, PI 153907, and PI 599386 suppressed 83 to 89% egg production relative to the susceptible control 'Beauregard', and these PIs were employed in subsequent experiments to determine if their efficacy against R. reniformis can be further increased by applying nonfumigant nematicides oxamyl, fluopyram, and fluensulfone. A 34 to 93% suppression of nematode reproduction was achieved by the application of nonfumigant nematicides, with oxamyl providing the best suppression followed by fluopyram and fluensulfone. Although sweetpotato cultivars resistant to R. reniformis are currently not available and there is a need for the development of safer yet highly effective nonfumigant nematicides, results from the current study suggest that complementing host plant resistance with nonfumigant nematicides can serve as an important tool for effective and sustainable nematode management.

Host-targeted Interventions as an Exciting Opportunity to Combat Malaria.

Terminal and benign diseases alike in adults, children, pregnant women, and others are successfully treated by pharmacological inhibitors that target human enzymes. Despite extensive global efforts to fight malaria, the disease continues to be a massive worldwide health burden, and new interventional strategies are needed. Current drugs and vector control strategies have contributed to the reduction in malaria deaths over the past 10 years, but progress toward eradication has waned in recent years. Resistance to antimalarial drugs is a substantial and growing problem. Moreover, targeting dormant forms of the malaria parasite Plasmodium vivax is only possible with two approved drugs, which are both contraindicated for individuals with glucose-6-phosphate dehydrogenase deficiency and in pregnant women. Plasmodium parasites are obligate intracellular parasites and thus have specific and absolute requirements of their hosts. Growing evidence has described these host necessities, paving the way for opportunities to pharmacologically target host factors to eliminate Plasmodium infection. Here, we describe progress in malaria research and adjacent fields and discuss key challenges that remain in implementing host-directed therapy against malaria.

The mechanism of host-induced germination in root parasitic plants.

Chemical signals known as strigolactones (SLs) were discovered more than 50 years ago as host-derived germination stimulants of parasitic plants in the Orobanchaceae. Strigolactone-responsive germination is an essential adaptation of obligate parasites in this family, which depend upon a host for survival. Several species of obligate parasites, including witchweeds (Striga, Alectra spp.) and broomrapes (Orobanche, Phelipanche spp.), are highly destructive agricultural weeds that pose a significant threat to global food security. Understanding how parasites sense SLs and other host-derived stimulants will catalyze the development of innovative chemical and biological control methods. This review synthesizes the recent discoveries of strigolactone receptors in parasitic Orobanchaceae, their signaling mechanism, and key steps in their evolution.

Immune selection suppresses the emergence of drug resistance in malaria parasites but facilitates its spread.

Although drug resistance in Plasmodium falciparum typically evolves in regions of low transmission, resistance spreads readily following introduction to regions with a heavier disease burden. This suggests that the origin and the spread of resistance are governed by different processes, and that high transmission intensity specifically impedes the origin. Factors associated with high transmission, such as highly immune hosts and competition within genetically diverse infections, are associated with suppression of resistant lineages within hosts. However, interactions between these factors have rarely been investigated and the specific relationship between adaptive immunity and selection for resistance has not been explored. Here, we developed a multiscale, agent-based model of Plasmodium parasites, hosts, and vectors to examine how host and parasite dynamics shape the evolution of resistance in populations with different transmission intensities. We found that selection for antigenic novelty ("immune selection") suppressed the evolution of resistance in high transmission settings. We show that high levels of population immunity increased the strength of immune selection relative to selection for resistance. As a result, immune selection delayed the evolution of resistance in high transmission populations by allowing novel, sensitive lineages to remain in circulation at the expense of the spread of a resistant lineage. In contrast, in low transmission settings, we observed that resistant strains were able to sweep to high population prevalence without interference. Additionally, we found that the relationship between immune selection and resistance changed when resistance was widespread. Once resistance was common enough to be found on many antigenic backgrounds, immune selection stably maintained resistant parasites in the population by allowing them to proliferate, even in untreated hosts, when resistance was linked to a novel epitope. Our results suggest that immune selection plays a role in the global pattern of resistance evolution.

Mechanisms and biological impacts of graphene and multi-walled carbon nanotubes on Drosophila melanogaster: Oxidative stress, genotoxic damage, phenotypic variations, locomotor behavior, parasitoid resistance, and cellular immune response.

The use of graphene and multi-walled carbon nanotubes (MWCNTs) has now become rather common in medical applications as well as several other areas thanks to their useful physicochemical properties. While in vitro testing offers some potential, in vivo research into toxic effects of graphene and MWCNTs could yield much more reliable data. Drosophila melanogaster has recently gained significant popularity as a dynamic eukaryotic model in examining toxicity, genotoxicity, and biological effects of exposure to nanomaterials, including oxidative stress, cellular immune response against two strains (NSRef and G486) of parasitoid wasp (Leptopilina boulardi), phenotypic variations, and locomotor behavior risks. D. melanogaster was used as a model organism in our study to identify the potential risks of exposure to graphene (thickness: 2-18 nm) and MWCNTs in different properties (as pure [OD: 10-20 nm short], modified by amide [NH2 ] [OD: 7-13 nm length: 55 µm], and modified by carboxyl [COOH] [OD: 30-50 nm and length: 0.5-2 µm]) at concentrations ranging from 0.1 to 250 µg/ml. Significant effects were observed at two high doses (100 and 250 µg/ml) of graphene or MWCNTs. This is the first study to report findings of cellular immune response against hematopoiesis and parasitoids, nanogenotoxicity, phenotypic variations, and locomotor behavior in D. melanogaster.

The molecular basis for peptide-based antimalarial vaccine development targeting erythrocyte invasion by P. falciparum.

This work describes a methodology for developing a minimal, subunit-based, multi-epitope, multi-stage, chemically-synthesised, anti-Plasmodium falciparum malaria vaccine. Some modified high activity binding peptides (mHABPs) derived from functionally relevant P. falciparum MSP, RH5 and AMA-1 conserved amino acid regions (cHABPs) for parasite binding to and invasion of red blood cells (RBC) were selected. They were highly immunogenic as assessed by indirect immunofluorescence (IFA) and Western blot (WB) assays and protective immune response-inducers against malarial challenge in the Aotus monkey experimental model. NetMHCIIpan 4.0 was used for predicting peptide-Aotus/human major histocompatibility class II (MHCII) binding affinity in silico due to the similarity between Aotus and human immune system molecules; ∼50% of Aotus MHCII allele molecules have a counterpart in the human immune system, being Aotus-specific, whilst others enabled recognition of their human counterparts. Some peptides' 1H-NMR-assessed structural conformation was determined to explain residue modifications in mHABPs inducing secondary structure changes. These directly influenced immunological behaviour, thereby highlighting the relationship with MHCII antigen presentation. The data obtained in such functional, immunological, structural and predictive approach suggested that some of these peptides could be excellent components of a fully-protective antimalarial vaccine.

Novel lactate dehydrogenase inhibitors with in vivo efficacy against Cryptosporidium parvum.

Cryptosporidium parvum is a highly prevalent zoonotic and anthroponotic protozoan parasite that causes a diarrheal syndrome in children and neonatal livestock, culminating in growth retardation and mortalities. Despite the high prevalence of C. parvum, there are no fully effective and safe drugs for treating infections, and there is no vaccine. We have previously reported that the bacterial-like C. parvum lactate dehydrogenase (CpLDH) enzyme is essential for survival, virulence and growth of C. parvum in vitro and in vivo. In the present study, we screened compound libraries and identified inhibitors against the enzymatic activity of recombinant CpLDH protein in vitro. We tested the inhibitors for anti-Cryptosporidium effect using in vitro infection assays of HCT-8 cells monolayers and identified compounds NSC158011 and NSC10447 that inhibited the proliferation of intracellular C. parvum in vitro, with IC50 values of 14.88 and 72.65 µM, respectively. At doses tolerable in mice, we found that both NSC158011 and NSC10447 consistently significantly reduced the shedding of C. parvum oocysts in infected immunocompromised mice's feces, and prevented intestinal villous atrophy as well as mucosal erosion due to C. parvum. Together, our findings have unveiled promising anti-Cryptosporidium drug candidates that can be explored further for the development of the much needed novel therapeutic agents against C. parvum infections.

ß-1,3-Glucan from Euglena gracilis as an immunostimulant mediates the antiparasitic effect against Mesanophrys sp. on hemocytes in marine swimming crab (Portunus trituberculatus).

ß-1,3-glucans, natural polysaccharide groups, exert immunomodulatory effects to improve the innate response and disease resistance in aquatic species and mammals. However, this ß-glucan stimulant is yet to be assayed in swimming crab (Portunus trituberculatus) hemocytes. In this study, we explored the immunomodulatory effect of ß-1,3-glucans (derived from Euglena gracilis) via in vitro 24 h stimulation assays in swimming crab hemocytes. We found that this algal ß-1,3-glucans in crab hemocytes significantly elevated cellular enzymes related parameters, including phenoloxidase (PO), lysozyme, acid phosphatase (ACP) activities, and superoxide anion generation (O2-) rate both at intracellular (P < 0.05) and extracellular (P < 0.05) levels. Besides, alkaline phosphatase (AKP) in hemocytes exhibited no significant differences across the groups (P > 0.05). ß-glucan significantly influenced (P < 0.05) the activities of the antioxidant enzyme, superoxide dismutase (SOD) in hemocytes. Moreover, the relative mRNA expression of numerous immune-related genes, including proPO, TLR-2, Alf-1, NOX, Lysozyme, Crustin-1, and Cuznsod, was significantly higher stimulated hemocytes than in control (P < 0.05). We also reported the dose-dependent antiparasitic activity against Mesanophyrs sp., in stimulated hemocytes than in the control (P < 0.05). The present study collectively demonstrated that ß-glucan potentially stimulates innate immunity by elevating cellular enzyme responses and up-regulating the mRNA expression of genes associated with crab innate immunity. Thus, ß-glucan is a promising immunostimulant for swimming crab farming in crustaceans aquaculture.

The Pupal Parasitoid Trichopria drosophilae Is Attracted to the Same Yeast Volatiles as Its Adult Host.

There is increasing evidence that microorganisms, particularly fungi and bacteria, emit volatile compounds that mediate the foraging behaviour of insects and therefore have the potential to affect key ecological relationships. However, to what extent microbial volatiles affect the olfactory response of insects across different trophic levels remains unclear. Adult parasitoids use a variety of chemical stimuli to locate potential hosts, including those emitted by the host's habitat, the host itself, and microorganisms associated with the host. Given the great capacity of parasitoids to utilize and learn odours to increase foraging success, parasitoids of eggs, larvae, or pupae may respond to the same volatiles the adult stage of their hosts use when locating their resources, but compelling evidence is still scarce. In this study, using Saccharomyces cerevisiae we show that Trichopria drosophilae, a pupal parasitoid of Drosophila species, is attracted to the same yeast volatiles as their hosts in the adult stage, i.e. acetate esters. Parasitoids significantly preferred the odour of S. cerevisiae over the blank medium in a Y-tube olfactometer. Deletion of the yeast ATF1 gene, encoding a key acetate ester synthase, decreased attraction of T. drosophilae, while the addition of synthetic acetate esters to the fermentation medium restored parasitoid attraction. Bioassays with individual compounds revealed that the esters alone were not as attractive as the volatile blend of S. cerevisiae, suggesting that other volatile compounds also contribute to the attraction of T. drosophilae. Altogether, our results indicate that pupal parasitoids respond to the same volatiles as the adult stage of their hosts, which may aid them in locating oviposition sites.

JAV1 controls jasmonate-regulated plant defense.

Plants evolve effective mechanisms to protect themselves from environmental stresses and employ jasmonates as vital defense signals to defend against insect attack and pathogen infection. Jasmonates are also recognized as an essential growth regulator by which diverse developmental processes are mediated. Despite substantial research, there are no key signaling components reported yet to control jasmonate-regulated plant defense independent of developmental responses. We identify JAV1, a key gene in the jasmonate pathway, which functions as a negative regulator to control plant defense but does not play a detectable role in plant development. Our results suggest that when encountering insect attack and pathogen infection, plants accumulate jasmonates that trigger JAV1 degradation via the 26S proteasome to activate defensive gene expression and elevate resistances against both insects and pathogens. These findings have provided insight into the molecular mechanism by which plants integrate jasmonate signals to protect themselves from insect attack and pathogen infection.

Molecular basis of strigolactone perception in root-parasitic plants: aiming to control its germination with strigolactone agonists/antagonists.

The genus Striga, also called "witchweed", is a member of the family Orobanchaceae, which is a major family of root-parasitic plants. Striga can lead to the formation of seed stocks in the soil and to explosive expansion with enormous seed production and stability once the crops they parasitize are cultivated. Understanding the molecular mechanism underlying the communication between Striga and their host plants through natural seed germination stimulants, "strigolactones (SLs)", is required to develop the technology for Striga control. This review outlines recent findings on the SL perception mechanism, which have been accumulated in Striga hermonthica by the similarity of the protein components that regulate SL signaling in nonparasitic model plants, including Arabidopsis and rice. HTL/KAI2 homologs were identified as SL receptors in the process of Striga seed germination. Recently, this molecular basis has further promoted the development of various types of SL agonists/antagonists as seed germination stimulants or inhibitors. Such chemical compounds are also useful to elucidate the dynamic behavior of SL receptors and the regulation of SL signaling.

Dose-dependent effects of antibiotic intake on Bombus Terrestris (Linnaeus, 1758) dietary intake, survival and parasite infection prevalence.

Diseases may contribute to the widespread declines seen in many bee species. The gut bacteria of bees may serve as one defence against disease, by preventing pathogen colonisation. However, exposure to antibiotics on forage or in the hive may disrupt bee gut bacteria and remove this protective effect. A number of studies show that high antibiotic doses reduce bee health but the effects of field-realistic antibiotic doses remain unclear. Here, we test how Bombus terrestris (Linnaeus, 1758) is affected by multiple field-realistic concentrations of the antibiotic oxytetracycline, which is sometimes used to protect flowering crops from bacterial infections. We measured survival, feeding behaviour and the likelihood of developing infection with the gut parasitic trypanosome Crithidia bombi Lipa & Triggiani, 1988 following oral inoculation with a range of antibiotic doses. Rising antibiotic concentrations were associated with reduced survival and food consumption, and an increased likelihood of becoming infected with C. bombi. These effects were seen at antibiotic concentrations that are applied to crops and so may be encountered by foraging bees in the field. These results support the hypothesis that field-realistic antibiotic doses have lethal and sub-lethal effects on B. terrestris and highlight the importance of improving our understanding of how field-realistic antibiotic doses affect pollinators.

Parasitism reduces oxidative stress of fish host experimentally exposed to PAHs.

Some parasites are known to bioaccumulate some environmental pollutants within their host. We hypothesized that these parasites may be beneficial for their hosts in polluted environments. We experimentally increased long-term (five weeks) exposure to polycyclic aromatic hydrocarbons (PAHs, three levels: 0.1X, 1X, 10X environmental exposure) in European chubs (Squalius cephalus) that were naturally infected or uninfected with acanthocephalan parasites. We monitored PAHs levels in fish tissues, as well as oxidative stress, telomere length and condition indices. Although parasite infection did not significantly reduce the levels of PAHs and PAH metabolites in host tissues, host oxidative status was explained by parasitism and pollution levels. Oxidative damage increased with parasitism in fish exposed to low PAH levels (0.1X) but decreased in infected fish at higher PAH exposure (10X), thus corroborating our hypothesis. Meanwhile, antioxidant capacity did not differ in response to parasite infection nor PAHs exposure. Despite this imbalance in oxidative status, experimental increase in PAH levels did not compromise telomere length, body condition, or survival in infected and uninfected fish. This study provides the first experimental evidence that the outcome of host-parasite interactions can shift from negative to positive as pollutant exposure increases.

Optimal Pest Control Strategies with Cost-effectiveness Analysis.

Pest and plant diseases cause damages and economic losses, threatening food security and ecosystem services. Thus, proper pest management is indispensable to mitigate the risk of losses. The risk of environmental hazards induced by toxic chemicals alongside the rapid development of chemical resistance by insects entails more resilient, sustainable, and ecologically sound approaches to chemical methods of control. This study evaluates the application of three dynamical measures of controls, namely, green insecticide, mating disruption, and the removal of infected plants, in controlling pest insects. A model was built to describe the interaction between plants and insects as well as the circulation of the pathogen. Optimal control measures are sought in such a way they maximize the healthy plant density jointly with the pests' density under the lowest possible control efforts. Our simulation study shows that all strategies succeed in controlling the insects. However, a cost-effectiveness analysis suggests that a strategy with two measures of green insecticide and plant removal is the most cost-effective, followed by one which applies all control measures. The best strategy projects the decrease of potential loss from 65.36% to 6.12%.

Targeting Parasite-Produced Macrophage Migration Inhibitory Factor as an Antivirulence Strategy With Antibiotic-Antibody Combination to Reduce Tissue Damage.

Targeting virulence factors represents a promising alternative approach to antimicrobial therapy, through the inhibition of pathogenic pathways that result in host tissue damage. Yet, virulence inhibition remains an understudied area in parasitology. Several medically important protozoan parasites such as Plasmodium, Entamoeba, Toxoplasma, and Leishmania secrete an inflammatory macrophage migration inhibitory factor (MIF) cytokine homolog, a virulence factor linked to severe disease. The aim of this study was to investigate the effectiveness of targeting parasite-produced MIF as combination therapy with standard antibiotics to reduce disease severity. Here, we used Entamoeba histolytica as the model MIF-secreting protozoan, and a mouse model that mirrors severe human infection. We found that intestinal inflammation and tissue damage were significantly reduced in mice treated with metronidazole when combined with anti-E. histolytica MIF antibodies, compared to metronidazole alone. Thus, this preclinical study provides proof-of-concept that combining antiparasite MIF-blocking antibodies with current standard-of-care antibiotics might improve outcomes in severe protozoan infections.

Insulin signalling in RBC is responsible for growth stimulation of malaria parasite in diabetes patients.

A cross-talk between diabetes and malaria within-host is well established. Diabetes is associated with modulation of the immune system, impairment of the healing process and to disturb the host metabolism to contribute towards propagation of parasite infection. Glucose metabolism in host is maintained by insulin and RBC has 2000 insulin receptor present on plasma membrane. These receptors are robust to relay down-stream signaling in RBCs but role of intracellular signaling in parasite growth is not been explored. The malaria parasite treated with insulin (100 ng/ml) is giving stimulation in parasite growth. The effect is lasting for several generations resulting into high parasitemia. Insulin signaling is phosphorylating protein in infected RBCs and level is high in parasite RBCs compared to uninfected RBCs. It is phosphorylating Spectrin-(α/ß), Band-4.2, Ankyrin and the other proteins of RBC cytoskeleton. It in-turn induces enhanced glucose uptake inside infected RBCs. There is a high level of infection of normal RBCs by merozoites. In summary, insulin and glucose metabolism plays a crucial role in parasite propagation, disease severity and need consideration while treating patients.

Inhibition of JNK signaling in the Asian malaria vector Anopheles stephensi extends mosquito longevity and improves resistance to Plasmodium falciparum infection.

Malaria is a global health concern caused by infection with Plasmodium parasites. With rising insecticide and drug resistance, there is a critical need to develop novel control strategies, including strategies to block parasite sporogony in key mosquito vector species. MAPK signaling pathways regulated by extracellular signal-regulated kinases (ERKs) and the stress-activated protein kinases (SAPKs) c-Jun N-terminal kinases (JNKs) and p38 MAPKs are highly conserved across eukaryotes, including mosquito vectors of the human malaria parasite Plasmodium falciparum. Some of these pathways in mosquitoes have been investigated in detail, but the mechanisms of integration of parasite development and mosquito fitness by JNK signaling have not been elucidated. To this end, we engineered midgut-specific overexpression of MAPK phosphatase 4 (MKP4), which targets the SAPKs, and used two potent and specific JNK small molecule inhibitors (SMIs) to assess the effects of JNK signaling manipulations on Anopheles stephensi fecundity, lifespan, intermediary metabolism, and P. falciparum development. MKP4 overexpression and SMI treatment reduced the proportion of P. falciparum-infected mosquitoes and decreased oocyst loads relative to controls. SMI-treated mosquitoes exhibited no difference in lifespan compared to controls, whereas genetically manipulated mosquitoes exhibited extended longevity. Metabolomics analyses of SMI-treated mosquitoes revealed insights into putative resistance mechanisms and the physiology behind lifespan extension, suggesting for the first time that P. falciparum-induced JNK signaling reduces mosquito longevity and increases susceptibility to infection, in contrast to previously published reports, likely via a critical interplay between the invertebrate host and parasite for nutrients that play essential roles during sporogonic development.

Investigation of 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one as a promising coumarin compound for the development of a new and orally effective antileishmanial agent.

Changes in host immunity and parasite resistance to drugs are among the factors that contribute to decreased efficacy of antiparasitic drugs such as the antimonial compounds pentamidine, amphotericin (AMP B) and miltefosine. Bioactive natural products could be alternatives for the development of new drugs to treat neglected human diseases such as leishmaniasis. Natural coumarins and synthetic analogues have shown leishmanicidal activity, mainly in vitro. This study investigated the in vitro and in vivo leishmanicidal activity of synthetic coumarin compounds (C1-C5) in parasites Leishmania (L.) amazonensis and L. (L.) infantum chagasi. The cytotoxicity of these compounds in mammalian cells and their influence on production of reactive oxygen species was also investigated. In vitro assays showed that 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one (C4) was as active as AMP B mainly in the amastigote form (p < 0.05); C4 presented a selectivity index (65.43) four times higher than C2 (15.4) in L. amazonensis and six times higher (33.94) than C1 (5.46) in L. infantum chagasi. Additionally, coumarin C4 reduced the H2O2 concentration 32.5% more than the control group in L. amazonensis promastigotes during the lag phase of proliferation. No interference of C4 was observed on the mitochondrial membrane potential of the parasites. In vivo, coumarin C4 in corn oil (oral route) led to a reduction in the number of amastigotes from L. infantum chagasi to 1.31 × 106 and 4.09 × 104 in the spleen and liver, respectively (p < 0.05). Thus, C4 represents a candidate for further studies aiming at new treatments of leishmaniasis.

Timing of sub-lethal insecticide exposure determines parasite establishment success in an insect-helminth model.

Environmental toxicants are pervasive in nature, but sub-lethal effects on non-target organisms and their parasites are often overlooked. Particularly, studies on terrestrial hosts and their parasites exposed to agricultural toxicants are lacking. Here, we studied the effect of sequence and timing of sub-lethal exposures of the pyrethroid insecticide alpha-cypermethrin on parasite establishment using the tapeworm Hymenolepis diminuta and its intermediate insect host Tenebrio molitor as a model system. We exposed T. molitor to alpha-cypermethrin (LD20) before and after experimental H. diminuta infection and measured the establishment success of larval tapeworms. Also, we conducted in vitro studies quantifying the direct effect of the insecticide on parasite viability. Our results showed that there was no direct lethal effect of alpha-cypermethrin on H. diminuta cysticercoids at relevant concentrations (LD10 to LD90 of the intermediate host). However, we observed a significantly increased establishment of H. diminuta in beetles exposed to alpha-cypermethrin (LD20) after parasite infection. In contrast, parasite establishment was significantly lower in beetles exposed to the insecticide before parasite infection. Thus, our results indicate that environmental toxicants potentially impact host-parasite interactions in terrestrial systems, but that the outcome is context-dependent by enhancing or reducing parasite establishment depending on timing and sequence of exposure.