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Parasite-induced surfacing in the cockle Austrovenus stuchburyi: adaptation or not?

Parasite manipulation of host behaviour is a compelling example of the extended phenotype. However, in many cases, such manipulation may be incorrectly assumed. Previous work has demonstrated that Austrovenus stuchburyi cockles stranded on mud-flat surfaces due to an inability to re-burrow both contain significantly more metacercariae of the trematode Curtuteria australis and are predated by the definitive host of this parasite at a faster rate than burrowed cockles. These results have been interpreted as strong evidence for a manipulation of cockle behaviour by the trematode to facilitate transmission to the definitive host. The model presented here, however, indicates that the selective advantage to the parasite of the altered host behaviour is currently of a negligible level at our study site that is highly unlikely to have been realized as an adaptation over evolutionary time. Hence, there are no grounds on which the more parsimonious explanation, that the altered host behaviour observed is simply an incidental side-effect of infection, can be rejected. We thus maintain that for any change in the behaviour of infected hosts to be confirmed as potentially a parasite trait that has evolved in response to selection, the adaptive benefit taking into account the entire parasite life cycle may need to be considered.

Adaptation, Physiological↗

Biology of the phylum nematomorpha.

Compared with most animal phyla, the Nematomorpha, also known as hair worms, is a relatively understudied metazoan phylum. Although nematomorphs make up only 1 of 3 animal phyla specializing solely on a parasitic life style, little attention has been focused on this enigmatic group scientifically. The phylum contains two main groups. The nectonematids are parasites of marine invertebrates such as hermit crabs. The gordiids are parasites of terrestrial arthropods, such as mantids, beetles, and crickets. Members of both of these groups are free-living as adults in marine and freshwaters respectively. In recent years, large strides have been made to understand this group more fully. New information has come from collection efforts, new approaches in organismal biology, modern techniques in microscopy and molecular biology. This review will focus on the advances made in four main areas of research: (1) morphology, (2) taxonomy and systematics, (3) life cycle and ecology and (4) host behavioural alterations. Recent research focus on the structure of both nectonematids and gordiids has added new insights on the morphology of adult worms and juveniles. The nervous system of gordiids is now well described, including the documentation of sensory cells. In addition, the availability of material from the juvenile of several species of gordiids has made it possible to document the development of the parasitic stage. New collections and reinvestigations of museum specimens have allowed for a critical reevaluation of the validity of established genera and species. However, traditional taxonomic work on this group continues to be hampered by two impeding factors: first is the lack of species-specific characters; and second is the problem of intraspecific variation, which has likely led to the description of numerous synonyms. Modern molecular techniques have been used recently to support independently the broad relationships among gordiids. During the turn of the millennium, the study of the life cycle and general ecology of gordiids enjoyed a revival. The pivotal outcome of this research was the domestication of a common American gordiid species, Paragordius varius. This species was the first of this phylum to be laboratory-reared. Through this research, the life cycle of several distantly related gordiid species was investigated. Other work showed that gordiids persist in the environment in the cyst stage by moving through different hosts by paratenesis. These cysts have been shown to retain infectivity for up to a year. These factors have likely contributed to the finding that gordiid cysts are one of the most common metazoans in some aquatic environments. Finally, recent work has focused on elucidating the mechanism of how gordiids make the transition from terrestrially based definitive hosts to a free-living aquatic environment. It has been shown that hosts are manipulated by the parasites to enter water. Using this study system, and using histology and proteomic tools, the method of manipulation used by these parasites is being further investigated. This manipulation, and the reaction of the cricket to this manipulation, has been postulated to benefit both the parasite and the host. Although large strides have been made within the last 10 years in the understanding of nematomorphs, we make the case that a lot of basic information remains to be uncovered. Although seemingly a daunting task, the recent advances in information and techniques lay a solid foundation for the future study of this unique group of parasites.

Animals↗

Differences among the three major strains of Toxoplasma gondii and their specific interactions with the infected host.

Toxoplasma gondii is one of the most successful protozoan parasites owing to its ability to manipulate the immune system and establish a chronic infection. There are many T. gondii strains but the majority identified in Europe and North America falls into three distinct clonal lineages. Many studies have investigated the ability of T. gondii to manipulate its host but few have examined directly whether the three lineages differ in this ability.

Animals↗

Modification of host cell apoptosis by viral and bacterial pathogens.

Bacterial and viral pathogens have evolved sophisticated strategies to manipulate the host cell's life span to their own advantage. This is achieved by modifications of the intrinsic apoptosis program at several checkpoints: kinases, caspases and mitochondria. The goal of this review is to give an overview over the molecular mechanisms involved.

Apoptosis↗

Application of emerging technologies in the antiviral field.

Viral diseases pose a serious threat to global public health, agriculture, and biosecurity. Conventional antiviral strategies are often limited by an incomplete understanding of disease mechanisms, poor targeting precision, and slow response times. Emerging technologies are now reshaping the landscape of antiviral research. This review examines the roles of four key frontiers, including organoid models, gene editing, AI-driven molecular design, and synthetic biology. Organoids provide physiologically relevant platforms that model virus-host interactions and disease progression. Viral infections remain a major challenge to human and animal health, agriculture, and biosecurity. Progress in antiviral research is constrained by the complexity of viral pathogenesis, the diversity and rapid evolution of viruses, and the limited translational relevance of some traditional model systems. Recent advances in organoid technology, gene editing, artificial intelligence, and synthetic biology are expanding the toolkit available for antiviral research and development. In this review, we discuss how these four technological frontiers contribute to disease modeling, target discovery, molecular design, and translational innovation. Organoids, in particular, provide physiologically relevant systems for investigating viral infection, tissue tropism, host responses, and pathogenesis. Gene editing tools, such as CRISPR, enable precise manipulation of host and viral genomes, facilitating the development of resistant organisms and next-generation vaccine platforms. AI technologies, including AlphaFold for structure prediction and platforms for de novo protein design, address long-standing bottlenecks in structural biology and offer powerful means to engineer antiviral proteins, antibodies, and vaccine antigens. Synthetic biology, guided by the Design-Build-Test-Learn cycle, integrates computational design, genetic assembly, and functional validation into a cohesive pipeline. Together, these technologies form a synergistic workflow that spans disease modeling, target discovery, molecular design, construction, testing, and iterative optimization. This integrated approach is shifting antiviral development from traditional empirical methods toward more precise, intelligent strategies. The review also highlights ongoing challenges in integration and scalability, stressing that high-quality biological datasets and stronger interdisciplinary collaboration are essential for realizing translational potential. By presenting a cohesive view of these converging methodologies, this review offers a framework to guide the intelligent evolution of antiviral strategies in both human and animal health.

Antiviral↗

A model of encounters between host and parasite populations.

A simulation model of the encounter between host and parasite populations is described. The model is two-dimensional in that it represents hosts and parasites as sums of random numbers. It allows for the manipulation of host and parasite numbers, areas of interaction, congruity of geographic ranges, parasite infectivity, and reproduction, or non-reproduction, of the parasite. The model generates parasite distributions (number of hosts vs. parasite/host classes) and their parameters (prevalence, mean number of parasites/host, variance/mean ratio as a measure of aggregation), and thus reveals the manner in which these parameters vary under different encounter conditions, i.e. their "behavior". Simulation results indicated that the behavior of parasite population mean, prevalence, and degree of aggregation was primarily a function of the rate at which infective stages were supplied to the system. In cases in which infective stages were continuously available, prevalence rose rapidly to nearly 100%, with increasing infectivity and parasite numbers, and the populations were not particularly aggregated. When infective stages were introduced in single large waves, both mean and prevalence remained low and the parasite populations were highly aggregated. Model results were compared with published data sets. The latter were also seen to fall into the two general categories of parameter behavior.

Animals↗

Immune modulation by a high molecular weight fraction from the rat tapeworm Hymenolepis diminuta.

The host-parasite relationship is exquisitely specific. In exploiting the host niche, a variety of helminth parasites have been shown to directly manipulate their hosts' immune responses. We assessed the ability of a whole-worm extract of Hymenolepis diminuta to modulate immune cell activation. Immune cells isolated from human blood or rodent spleens were activated with the T cell mitogen, concanavalin A (Con A) +/- H. diminuta extract and cytokine production (i.e. IL-2, -4, -10, -12) and proliferation assessed by ELISA and [3H]thymidine incorporation 24 and 72 h post-treatment, respectively. Co-treatment with the H. diminuta extract (100 microg protein/ml) virtually abolished Con A-induced immune cell proliferation, which was not due to increased apoptosis. Boiling of the worm extract reduced its anti-proliferative effect and fractionation indicated that a > 50 kDa component was predominantly responsible for the inhibition of Con A-induced immune cell proliferation. Cytokine determinations revealed that the H. diminuta extract significantly reduced Con A-stimulated IL-2 and IL-4, but enhanced the production of IFNy, IL-12 and IL-10. The increased IL-12 was due to an LPS contaminant in the extract and a helminth-derived 'IL-12'-like peptide that bound in the ELISA and Western blots. In contrast, a H. diminuta-derived factor directly stimulated IL-10 production by murine splenocytes, and contaminating LPS synergistically enhanced the production of IL-10. Thus, H. diminuta has the potential to block stimulated T cell proliferation and, by inhibiting IL-4 and promoting IL-10 production, may bias the immune environment towards one of immunoregulation and away from IL-4 dominated T helper 2 type events.

Animals↗

Impairment of the chemical defence of the beetle, Tenebrio molitor, by metacestodes (cysticeroids) of the tapeworm, Hymenolepis diminuta.

The defensive glands of beetles, Tenebrio molitor, infected with metacestodes (cysticercoids) of Hymenolepis diminuta are everted less frequently upon stimulation, and contain less toluquinone (methylbenzoquinone) and m-cresol, than glands of uninfected controls. These differences, as shown in predation trials with wild rats, increase the likelihood that both cysticercoids and beetles will be ingested by the tapeworm's definitive host. This is the first documented case of a parasite inhibiting the chemical defence of an intermediate host, and one of only a few reports of parasite-induced manipulation of host biology supported by empirical evidence implicating facilitated parasite transmission between host species.

Animals↗

Glucosinolate genetics and the attraction of the aphid parasitoid Diaeretiella rapae to Brassica.

The control of insect pests using parasitoids and carnivores has been successfully applied in protected cropping systems, orchards and forestry. Their success in annual field crops has been more limited due largely to the difficulties of attracting and maintaining a sufficient density of parasitoids in the crop before the levls of the insect herbivores become economically damaging. Parasitoids are known to be attracted to host-plant volatiles; thus, manipulating the host-plant chemistry may provide a means of enhancing the attraction of parasitoids to their prey. In this study we describe the differential attraction of the braconid wasp Diaeretiella rapae to two near-isogenic lines of Brassica oleracea which differ in a gene which alters the chemical structure of the isothiocyanates which are emitted following tissue damage. We demonstrate that, by enhancing the production of but-3-enyl isothiocyanate in B. oleracea and Brassica napus (oilseed rape), we can increase the attraction of D. rapae to these plants under standard field conditions.

Animals↗

Domain switching and host recognition.

The collective function of secreted pathogen effector molecules is to enhance the virulence and avirulence activity of the pathogen during the infection of its host. While the activity of a majority of pathogen effectors is unknown, several classes of effector molecules have been well characterized. Among these include proteins which function to modulate host defences either through proteolysis, post-translational modifications, or by directly manipulating the host transcriptional machinery that regulates the induction of defence responses. In recent years, several key advances have been made in the characterization of the latter class of effector molecules. Among these include research characterizing the processes associated with host nuclear import and the targeting of host transcriptional defences. While current research is beginning to reveal the biochemical and genetic mechanisms controlling the induction of host resistance, the signalling events that control host specificity remain largely unknown. In this issue of Molecular Microbiology, work by Nissan et al. sheds light onto the molecular-genetic patterns involved in determining host specificity and pathogen virulence in the Pantoea-gypsophila interaction.

Bacterial Proteins↗

Infection with Toxoplasma gondii bradyzoites has a diminished impact on host transcript levels relative to tachyzoite infection.

Toxoplasma gondii, an intracellular pathogen, has the potential to infect nearly every warm-blooded animal but rarely causes morbidity. The ability for the parasite to convert to the bradyzoite stage and live inside slow-growing cysts that can go unnoticed by the host immune system allows for parasite persistence for the life of the infected host. This intracellular survival likely necessitates host cell modulation, and tachyzoites are known to modify a number of signaling cascades within the host to promote parasite survival. Little is known, however, about how bradyzoites manipulate their host cell. Microarrays were used to profile the host transcriptional changes caused by bradyzoite infection and compared to those of tachyzoite-infected and uninfected hosts cells 2 days postinfection in vitro. Infection resulted in chemokine, cytokine, extracellular matrix, and growth factor transcript level changes. A small group of genes were specifically induced by tachyzoite infection, including granulocyte-macrophage colony-stimulating factor, BCL2-related protein A1, and interleukin-24. Bradyzoite infection yielded only about half the changes seen with tachyzoite infection, and those changes that did occur were almost all of lower magnitude than those induced by tachyzoites. These results suggest that bradyzoites lead a more stealthy existence within the infected host cell.

Animals↗

Transfected Plasmodium knowlesi produces bioactive host gamma interferon: a new perspective for modulating immune responses to malaria parasites.

Transgenic pathogenic microorganisms expressing host cytokines such as gamma interferon (IFN-gamma) have been shown to manipulate host-pathogen interaction, leading to immunomodulation and enhanced protection. Expression of host cytokines in malaria parasites offers the opportunity to investigate the potential of an immunomodulatory approach by generating immunopotentiated parasites. Using the primate malaria parasite Plasmodium knowlesi, we explored the conditions for expressing host cytokines in malaria parasites. P. knowlesi parasites transfected with DNA constructs for expressing rhesus monkey (Macaca mulatta) IFN-gamma under the control of the heterologous P. berghei apical membrane antigen 1 promoter, produced bioactive IFN-gamma in a developmentally regulated manner. IFN-gamma expression had no marked effect on in vitro parasite development. Bioactivity of the parasite-produced IFN-gamma was shown through inhibition of virus cytopathic effect and confirmed by using M. mulatta peripheral blood cells in vitro. These data indicate for the first time that it is feasible to generate malaria parasites expressing bioactive host immunomodulatory cytokines. Furthermore, cytokine-expressing malaria parasites offer the opportunity to analyze cytokine-mediated modulation of malaria during the blood and liver stages of the infection.

Animals↗

Signal sequence analysis of expressed sequence tags from the nematode Nippostrongylus brasiliensis and the evolution of secreted proteins in parasites.

BACKGROUND: Parasitism is a highly successful mode of life and one that requires suites of gene adaptations to permit survival within a potentially hostile host. Among such adaptations is the secretion of proteins capable of modifying or manipulating the host environment. Nippostrongylus brasiliensis is a well-studied model nematode parasite of rodents, which secretes products known to modulate host immunity. RESULTS: Taking a genomic approach to characterize potential secreted products, we analyzed expressed sequence tag (EST) sequences for putative amino-terminal secretory signals. We sequenced ESTs from a cDNA library constructed by oligo-capping to select full-length cDNAs, as well as from conventional cDNA libraries. SignalP analysis was applied to predicted open reading frames, to identify potential signal peptides and anchors. Among 1,234 ESTs, 197 (~16%) contain predicted 5' signal sequences, with 176 classified as conventional signal peptides and 21 as signal anchors. ESTs cluster into 742 distinct genes, of which 135 (18%) bear predicted signal-sequence coding regions. Comparisons of clusters with homologs from Caenorhabditis elegans and more distantly related organisms reveal that the majority (65% at P < e-10) of signal peptide-bearing sequences from N. brasiliensis show no similarity to previously reported genes, and less than 10% align to conserved genes recorded outside the phylum Nematoda. Of all novel sequences identified, 32% contained predicted signal peptides, whereas this was the case for only 3.4% of conserved genes with sequence homologies beyond the Nematoda. CONCLUSIONS: These results indicate that secreted proteins may be undergoing accelerated evolution, either because of relaxed functional constraints, or in response to stronger selective pressure from host immunity.

Animals↗

Broad-host range expression vectors containing manipulated meta-cleavage pathway regulatory elements of the TOL plasmid.

The construction of pERD20 and pERD21, two broad-host range expression vectors, is described. The vectors contain the Pm promoter of the meta-cleavage pathway operon of the TOL plasmid pWWO; this promoter is present within a polylinker which provides a number of downstream cloning sites close to the transcription initiation site. Transcription from the Pm promoter in these vectors is controlled not by the natural positive regulator of Pm, the Xy1S protein, but by an Xy1S mutant analogue, Xy1S2tr6, which inhibits an altered effector specificity and can mediate a 3-8-fold higher level of transcription than can Xy1S in a wide range of temperatures. Controlled expression of cloned genes can be achieved in a broad spectrum of Gram negative bacteria grown at a wide range of temperatures.

Alleles↗

Physiological cost induced by the maternally-transmitted endosymbiont Wolbachia in the Drosophila parasitoid Leptopilina heterotoma.

Endosymbiotic bacteria of the genus Wolbachia infect a number of invertebrate species in which they induce various alterations in host reproduction, mainly cytoplasmic incompatibility (CI). In contrast to most other maternally transmitted parasites, manipulation of host reproduction makes the spread of Wolbachia possible even if they induce a physiological cost on their hosts. Current studies have shown that fitness consequences of Wolbachia infection could range from positive (mutualist) to negative (parasitic) but, in most cases, Wolbachia do not have strong deleterious effects on host fitness and the status of association remains unclear. Here, we show that in the Drosophila parasitoid wasp Leptopilina heterotoma, Wolbachia infection has a negative impact on several host fitness traits of both sexes. Fecundity, adult survival and locomotor performance are significantly reduced, whereas circadian rhythm, development time and offspring sex-ratio are not affected. Although the cost of bacterial infection can be overcome by effects on host reproduction i.e. cytoplasmic incompatibility, it could influence the spread of the bacterium at the early stages of the invasion process. Clearly, results underline the wide spectrum of phenotypic effects of Wolbachia infection and, to our knowledge, Wolbachia infection of L. heterotoma appears to be one of the most virulent that has ever been observed in insects.

Animals↗

Sexually transmitted diseases of insects: distribution, evolution, ecology and host behaviour.

Sexually transmitted diseases (STDs) of insects are known from the mites, nematodes, fungi, protists and viruses. In total 73 species of parasite and pathogen from approximately 182 species of host have been reported. Whereas nearly all vertebrate STDs are viruses or bacteria, the majority of insect STDs are multicellular ectoparasites, protistans or fungi. Insect STDs display a range of transmission modes, with 'pure' sexual transmission only described from ectoparasites, all of which are mites, fungi or nematodes, whereas the microparasitic endo-parasites tend to show vertical as well as sexual transmission. The distribution of STDs within taxa of insect hosts appears to be related to the life histories of the hosts. In particular, STDs will not be able to persist if host adult generations do not overlap unless they are also transmitted by some alternative route. This explains the observation that the Coleoptera seem to suffer from more STDs than other insect orders, since they tend to diapause as adults and are therefore more likely to have overlapping generations of adults in temperate regions. STDs of insects are often highly pathogenic, and are frequently responsible for sterilizing their hosts, a feature which is also found in mammalian STDs. This, combined with high prevalences indicates that STDs can be important in the evolution and ecology of their hosts. Although attempts to demonstrate mate choice for uninfected partners have so far failed it is likely that STDs have other effects on host mating behaviour, and there is evidence from a few systems that they might manipulate their hosts to cause them to mate more frequently. STDs may also play a part in sexual conflict, with males in some systems possibly gaining a selective advantage from transmitting certain STDs to females. STDs may well be important factors in host population dynamics, and some have the potential to be useful biological control agents, but empirical studies on these subjects are lacking.

Animals↗

Manipulation of fifth-instar host (Manduca sexta) ecdysteroid levels by the parasitoid wasp Cotesia congregata.

Although 5th (last) instar parasitized Manduca sexta larvae undergo developmental arrest and do not wander, they exhibit a small hemolymph ecdysteroid peak (300-400pg/&mgr;l) which begins one day prior to the parasitoid's molt to the 3rd (last) instar and concomitant emergence from the host. Ecdysteroids present in this peak were 20-hydroxyecdysone, 20,26-dihydroxyecdysone and one or more very polar ecdysteroids, as well as small amounts of 26-hydroxyecdysone and ecdysone. In parasitized day-1 and -2 5th instars ligated just behind the 1st abdominal proleg, hemolymph ecdysteroid levels increased in both anterior and posterior portions (100-500pg/&mgr;l), while in unparasitized larvae, hormone levels only increased in the anterior portion (100-350pg/&mgr;l). Thus, the ecdysteroid peak observed in host 5th instars was probably produced, at least in part, by the parasitoids. It may serve to promote Cotesia congregata's molt from the second to the third instar and/or to facilitate parasitoid emergence from the host. In parasitized day-1 and -2 5th instars ligated between the last thoracic and 1st abdominal segments, hemolymph ecdysteroid titers reached much higher levels (500-3500pg/&mgr;l) in the anterior portion (no parasitoids present) than in the posterior portion (150-450pg/&mgr;l). Therefore, it appears that the parasitoid's regulation of hemolymph ecdysteroid titers occurs at two levels. First, parasitization neutralizes the host's ability to maintain its normal hemolymph ecdysteroid levels. Second, in a separate action, the parasitoid manipulates the ecdysteroid-producing machinery so that hemolymph levels are maintained at the 200-400pg/&mgr;l characteristic of day 3-4 hosts. This is the first report of a parasitoid's ability to interfere with the normal inhibitory mechanisms which prevent prothoracic gland production of ecdysteroid at inappropriate periods of insect growth and development.

Journal Article↗

HIV accessory proteins and surviving the host cell.

Human immunodeficiency virus generates the accessory proteins Nef, viral infectivity factor (Vif), viral protein R, and viral protein U or viral protein X during viral replication in host cells. Although the significance of these accessory proteins is often lost in vitro, they are essential for viral pathogenesis in vivo. Therefore, these proteins have much potential as antiviral targets. Recent data reveal Vif perturbs an ill-defined antiviral pathway in host cells allowing HIV replication. These data highlight a common feature among HIV accessory proteins in manipulating the host to aid viral pathogenesis. Therefore, these new insights into Vif and other HIV accessory proteins are reviewed, emphasizing host cell interactions and new targets for therapeutic intervention.

HIV Infections↗