Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. Traditional antigens for serological diagnosis include several members of the trans-sialidase (TS) protein superfamily, which have roles in host-paras...Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. Traditional antigens for serological diagnosis include several members of the trans-sialidase (TS) protein superfamily, which have roles in host-parasite interactions and elicit strong B cell responses. T. cruzi expresses a large TS repertoire, comprising over 3200 polymorphic genes, organized into eight subfamilies based on sequence motifs and functional characteristics. These proteins are known to facilitate infection and immune evasion. Multiple TS antigens from different subfamilies elicit strong immune responses, with a growing list from recent studies. Current diagnostic assays still rely on antigens discovered decades ago. This review article aims to cover the immunodominance of the TS protein superfamily and their use as antigens for the serological diagnosis of Chagas disease.
Timely identification of resistance to antimalarials is necessary to ensure effective malaria case management. The backbone of antimalarial resistance surveillance strategies is the therapeutic efficacy study (TES). Orig...Timely identification of resistance to antimalarials is necessary to ensure effective malaria case management. The backbone of antimalarial resistance surveillance strategies is the therapeutic efficacy study (TES). Originally designed to be easily deployable, in recent years, TES have become increasingly complex and slow to yield results. Concurrently, advances in molecular surveillance techniques, the emergence and spread of artemisinin partial resistance in Africa, and advances in antimalarial drug stewardship through multiple first-line therapies have changed the context in which TES are implemented. In this opinion article, we outline considerations for recalibrating TES methodology. More efficient TES, coupled with molecular surveillance, could provide timely and actionable data for malaria-endemic countries as they manage treatment policies in the context of drug resistance in Africa.
Male regulation of female reproductive development in schistosomes depends on an intact reproductive neural network. You et al. identify a limbic system-associated membrane protein as essential for maintaining this netwo...Male regulation of female reproductive development in schistosomes depends on an intact reproductive neural network. You et al. identify a limbic system-associated membrane protein as essential for maintaining this network, enabling the efficient release of the pheromone β-alanyl-tryptamine dipeptide, which promotes female maturation.
Cryptosporidium is a leading cause of severe diarrheal disease, for which effective treatments and vaccines are lacking. The past decade has seen breakthrough advances in how the parasite and disease can be studied in th...Cryptosporidium is a leading cause of severe diarrheal disease, for which effective treatments and vaccines are lacking. The past decade has seen breakthrough advances in how the parasite and disease can be studied in the field and the laboratory. This has led to an increasingly molecular understanding of how parasite protein secretion orchestrates invasion and host-parasite interactions and to a revision of the Cryptosporidium life cycle. Parasite sex emerges as an engine of genomic innovation, allowing the parasite to adaptively evolve host specificity, virulence, and drug resistance. The unique importance of sex for Cryptosporidium also offers opportunities for forward genetic discovery and could provide new targets for treatment and prevention. Here, we review key concepts and discuss the outstanding questions critical to fundamental understanding and translational advancement.
Beyond genetics and immunity, the gut microbiome may be an underappreciated determinant of malaria parasite burden. Gustin et al. demonstrated that pre-infection microbiome composition predicts the level of Plasmodium pa...Beyond genetics and immunity, the gut microbiome may be an underappreciated determinant of malaria parasite burden. Gustin et al. demonstrated that pre-infection microbiome composition predicts the level of Plasmodium parasitemia in both rhesus macaques and human volunteers, with convergent evidence pointing to Bifidobacterium as a potentially protective genus.
Zhang et al. provide the first global synthesis of 230 emerging tick-borne viruses, introducing a genomic model that predicts zoonotic risk. Their approach identifies 25 very-high-risk viruses and clinically validates th...Zhang et al. provide the first global synthesis of 230 emerging tick-borne viruses, introducing a genomic model that predicts zoonotic risk. Their approach identifies 25 very-high-risk viruses and clinically validates three novel human pathogens, shifting the paradigm from reactive discovery to proactive risk assessment for global health security.
Malaria remains a global health crisis, exacerbated by the rise of drug-resistant strains of Plasmodium species to clinically used drugs, as well as newly developed therapeutic agents. Historically, natural-product-deriv...Malaria remains a global health crisis, exacerbated by the rise of drug-resistant strains of Plasmodium species to clinically used drugs, as well as newly developed therapeutic agents. Historically, natural-product-derived drugs such as quinine and artemisinin have been the cornerstones of malaria treatment, distinguished by their ability to attack the parasite on multiple fronts simultaneously. This review explores the paradigm of single drugs with multiple targets, a polypharmacology strategy designed to achieve combination-therapylike efficacy within a single compound. We discuss how natural products leverage multitarget mechanisms of action, reducing the likelihood of resistance, and the opportunities and challenges in developing next-generation antimalarials. Understanding and harnessing polypharmacology in antimalarial drug design could prolong therapeutic durability and reinvigorate our arsenal against malaria.
Parasitoid wasps are a remarkably diverse group of insects that employ intricate parasitic strategies. Their reproductive success largely depends on their ability to precisely manipulate their hosts. The Drosophila-paras...Parasitoid wasps are a remarkably diverse group of insects that employ intricate parasitic strategies. Their reproductive success largely depends on their ability to precisely manipulate their hosts. The Drosophila-parasitoid wasp system is a powerful model for deciphering the mechanisms underlying such host manipulation. Here, we summarize the known species of Drosophila parasitoid wasps and their molecular tools, focusing on genome resources and key parasitic effectors such as venom. We also discuss the molecular mechanisms revealed through these tools that underpin the manipulation of host immunity, nutrition, development, and behavior. Finally, we emphasize that expanding research to a broader range of parasitoid wasp lineages is essential for deepening our mechanistic understanding and advancing their potential in biocontrol applications.
Microsporidia are obligate intracellular parasites that can infect various invertebrate and vertebrate species, including humans. They have evolved resistance strategies to survive in their ecological niche. When dormant...Microsporidia are obligate intracellular parasites that can infect various invertebrate and vertebrate species, including humans. They have evolved resistance strategies to survive in their ecological niche. When dormant, microsporidia exist in the form of spores to withstand harsh environmental stressors and conserve energy. When stimulated by appropriate conditions, microsporidia germinate and inject infective sporoplasm into host cells, hijacking host metabolism to acquire energy and utilizing multiple strategies to regulate and evade host defense, manipulate the host cytoskeleton, and proliferate successfully. In this review, we summarize microsporidia resistance strategies and escape mechanisms that enable them to overcome host- and environment-imposed challenges. Such insights advance our understanding of microsporidia biology and host-pathogen interactions.
In this review, we tell the story of how two related parasites that belong to the same genus, Trypanosoma brucei and Trypanosoma cruzi, cause very distinct lethal diseases and how γδ T cells help shape these outcomes. It...In this review, we tell the story of how two related parasites that belong to the same genus, Trypanosoma brucei and Trypanosoma cruzi, cause very distinct lethal diseases and how γδ T cells help shape these outcomes. It synthesizes current knowledge on γδ T-cell responses to T. brucei and T. cruzi, highlighting shared and parasite-specific features. Here we emphasize how γδ T-cell cytotoxic versus regulatory programs and tissue residency in blood, lymphoid organs, liver, gut, heart, and skin influence early parasite control, chronic persistence, and immunopathology. Finally, we discuss the gaps that need to be filled and how these insights may inform new interventions, including modulation of γδ function, γδ-targeted vaccine strategies, and γδ-based biomarkers for host-directed therapies in Chagas disease and human African trypanosomiasis.
Insects have formed close relationships with endosymbiotic microorganisms, enabling adaptation and promoting diversification. In this review, we examined studies of endosymbiotic bacteria in parasitic lice (Psocodea: Pht...Insects have formed close relationships with endosymbiotic microorganisms, enabling adaptation and promoting diversification. In this review, we examined studies of endosymbiotic bacteria in parasitic lice (Psocodea: Phthiraptera). Lice and their endosymbionts lead fairly secluded lives, with each louse-host and louse-endosymbiont pair evolving in relative isolation. Consequently, each louse lineage and its associated endosymbiont represents natural replicates, useful for understanding how endosymbiosis arises and evolves under similar ecological conditions. While louse endosymbionts are vertically transmitted, they show surprisingly low levels of cospeciation with their louse hosts. Instead, phylogenomic evidence indicates repeated, independent acquisitions of endosymbionts from free-living progenitors. Following each acquisition, endosymbiont lineages experienced elevated evolutionary rates and genomic reduction, losing functionally redundant pathways while retaining functions necessary to maintain the symbiosis.
Trends Parasitol
· 2026 Apr · PMID 41820076
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Wendt and Collins identify a cyclin-dependent kinase inhibitor (cki) in Schistosoma mansoni that, along with p53-1 (schistosome homolog of TP-53), suppresses tegument cell proliferation. Knockdown of cki causes hyperprol...Wendt and Collins identify a cyclin-dependent kinase inhibitor (cki) in Schistosoma mansoni that, along with p53-1 (schistosome homolog of TP-53), suppresses tegument cell proliferation. Knockdown of cki causes hyperproliferation and, together with p53-1 loss, tumorlike growths. Homologs of cki are widespread in parasitic flatworms but absent in free-living relatives, suggesting that the horizontal gene transfer aided the evolution of parasitism.
Polymerase chain reaction (PCR) plays a central role in parasite diagnostics but is increasingly interpreted as a general test for parasitic infection. Because parasites lack shared molecular features amenable to univers...Polymerase chain reaction (PCR) plays a central role in parasite diagnostics but is increasingly interpreted as a general test for parasitic infection. Because parasites lack shared molecular features amenable to universal assays, PCR is inherently primer bounded and hypothesis confirming. This article clarifies the interpretive limits of PCR and argues for aligning diagnostic claims with parasite biology.
Independent protein-protein interaction networks in kinetoplastid parasites show little overlap, often interpreted as biological divergence. We argue that this pattern largely reflects fragmented sampling. Integrating in...Independent protein-protein interaction networks in kinetoplastid parasites show little overlap, often interpreted as biological divergence. We argue that this pattern largely reflects fragmented sampling. Integrating interactomes from Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donovani improves functional coverage and interpretability while preserving lineage-specific assemblies, providing a framework for hypothesis generation across species.
No vaccines are currently available for any gastrointestinal nematode (GIN) infections of humans, despite a large global burden of disease. In livestock, limited helminth vaccines are available, while current anthelminti...No vaccines are currently available for any gastrointestinal nematode (GIN) infections of humans, despite a large global burden of disease. In livestock, limited helminth vaccines are available, while current anthelmintic treatments are waning in their effectiveness as resistance is developing. The reasons for the lack of vaccines are manifold but include the complexity of the parasite genomes, the lack of defined correlates of protection, and the immunomodulatory activities of GIN infections. In recent years, our knowledge of parasite immunomodulation has dramatically advanced. Here, we propose that vaccination approaches can be used to block either parasite immunomodulation or digestive processes, allowing effective ejection or starvation of these parasites. We compare this approach to vaccines against other pathogens and summarise data from rodent, livestock, and human infections.