Manipulate Host Behaviour Research Articles

Mechanisms Underlying Ophiocordyceps Infection and Behavioral Manipulation of Ants: Unique or Ubiquitous?

Parasite manipulation of host behavior, as an effective strategy to establish transmission, has evolved multiple times across taxa, including fungi. Major strides have been made to propose molecular mechanisms that underlie manipulative parasite-host interactions including the manipulation of carpenter ant behavior by Ophiocordyceps. This research suggests that the secretion of parasite proteins and light-driven biological rhythms are likely involved in the infection and manipulation biology of Ophiocordyceps and other manipulating parasites. Here, we discuss research on Ophiocordyceps considering findings from other (fungal) parasites that either are relatively closely related (e.g., other insect- and plant-infecting Hypocreales) or also manipulate insect behavior (e.g., Entomophthorales). As such, this review aims to put forward this question: Are the mechanisms behind Ophiocordyceps manipulation and infection unique, or did they convergently evolve? From this discussion, we pose functional hypotheses about the infection biology of Ophiocordyceps that will need to be addressed in future studies.

Neurotransmitter acetylcholine mediates the mummification of Ophiocordyceps sinensis-infected Thitarodes xiaojinensis larvae.

Parasites can manipulate host behavior to facilitate parasite transmission. One such host-pathogen interaction occurs between the fungus Ophiocordyceps sinensis and the ghost moth Thitarodes xiaojinensis. O. sinensis is involved in the mummification process of infected host larvae. However, the underlying molecular and chemical mechanism for this phenomenon is unknown. We characterized the small molecules regulating host behaviors and the altered metabolites in infected and mummified host larvae. Lipid-related metabolites, such as phosphatidylcholine, were identified in infected and mummified larvae. Decreased levels of the neurotransmitter acetylcholine (ACh) and elevated choline levels were observed in the brains of both the infected and mummified larvae. The aberrant activity of acetylcholinesterase (AChE) and relative mRNA expression of ACE2 (acetylcholinesterase) may mediate the altered transformation between ACh and choline, leading to the brain dysfunction of mummified larvae. Caspofungin treatment inhibited the mummification of infected larvae and the activity of AChE. These findings indicate the importance of ACh in the mummification of host larvae after O. sinensis infection.IMPORTANCEOphiocordyceps sinensis-infected ghost moth larvae are manipulated to move to the soil surface with their heads up in death. A fruiting body then grows from the caterpillar's head, eventually producing conidia for dispersal. However, the underlying molecular and chemical mechanism has not been characterized. In this study, we describe the metabolic profile of Thitarodes xiaojinensis host larvae after O. sinensis infection. Altered metabolites, particularly lipid-related metabolites, were identified in infected and mummified larvae, suggesting that lipids are important in O. sinensis-mediated behavioral manipulation of host larvae. Decreased levels of the neurotransmitter acetylcholine were observed in both infected and mummified larvae brains. This suggests that altered or reduced acetylcholine can mediate brain dysfunction and lead to aberrant behavior. These results reveal the critical role of acetylcholine in the mummification process of infected host larvae.

Echinococcus multilocularis infection affects risk-taking behaviour in Microtus arvalis: adaptive manipulation?

Manipulation of host behaviour by parasites to enhance transmission to the next host is a fascinating phenomenon that has interested scientists since the 1970s. It has been proposed that infection with the cestode Echinococcus multilocularis produces an impairment of the antipredatory behaviour in the rodent intermediate host common vole, Microtus arvalis, which may facilitate transmission of the tapeworm to the canid final host. In this study, we observed the behaviour of infected common voles at 12 weeks post-infection, when protoscoleces production and maturation commonly occurs, in order to assess behavioural changes compared to uninfected controls, that might ease predation in the wild. Infected and uninfected voles were monitored for 24 h to observe their spontaneous activity. In addition, the next day, both infected and uninfected voles were subjected to 4 different behavioural tests: open field test, barrier test, platform test and air-puff test in a running wheel. No significant difference between uninfected and infected voles emerged during the behavioural tests. However, observation of spontaneous activity revealed that infected voles increased their feeding frequency and spent significantly more time above bedding even when not eating, compared to the uninfected controls. In the wild, these behavioural changes increase the animals exposure to predators, raising their chance of becoming prey. These findings are the first direct evidence consistent with behavioural manipulation by E. multilocularis on common voles.

Baculovirus entry into the central nervous system of Spodoptera exigua caterpillars is independent of the viral protein tyrosine phosphatase.

Neuroparasitism concerns the hostile take-over of a host's nervous system by a foreign invader, in order to alter the behaviour of the host in favour of the parasite. One of the most remarkable cases of parasite-induced host behavioural manipulation comprises the changes baculoviruses induce in their caterpillar hosts. Baculoviruses may manipulate caterpillar behaviour in two ways: hyperactivity (increased movement in the horizontal plane) and/or tree-top disease (movement to elevated levels in the vertical plane). Those behavioural changes are followed by liquefaction and death of the caterpillar. In Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-infected Spodoptera exigua caterpillars, an enzymatic active form of the virally encoded protein tyrosine phosphatase (PTP) is needed for the expression of hyperactivity from 3 days post infection (dpi). Using eGFP-expressing recombinant AcMNPV strains, we show that infection of the caterpillar's central nervous system (CNS) can be observed primarily from 3 dpi onwards. In addition, we demonstrate that the structural and enzymatic function of PTP does not play a role in infection of the CNS. Instead we show that the virus entered the CNS via the trachea, progressing caudally to frontally through the CNS and that the infection progressed from the outermost cell layers towards the inner cell layers of the CNS, in a PTP independent manner. These findings help to further understand parasitic manipulation and the mechanisms by which neuroparasites infect the host nervous system to manipulate host behaviour.

Massive horizontal gene transfer and the evolution of nematomorph-driven behavioral manipulation of mantids

To complete their life cycle, a wide range of parasites must manipulate the behavior of their hosts.1 This manipulation is a well-known example of the "extended phenotype,2" where genes in one organism have phenotypic effects on another organism. Recent studies have explored the parasite genes responsible for such manipulation of host behavior, including the potential molecular mechanisms.3,4 However, little is known about how parasites have acquired the genes involved in manipulating phylogenetically distinct hosts.4 In a fascinating example of the extended phenotype, nematomorph parasites have evolved the ability to induce their terrestrial insect hosts to enter bodies of water, where the parasite then reproduces. Here, we comprehensively analyzed nematomorphs and their mantid hosts, focusing on the transcriptomic changes associated with host manipulations and sequence similarity between host and parasite genes to test molecular mimicry. The nematomorph's transcriptome changed during host manipulation, whereas no distinct changes were found in mantids. We then discovered numerous possible host-derived genes in nematomorphs, and these genes were frequently up-regulated during host manipulation. Our findings suggest a possible general role of horizontal gene transfer (HGT) in the molecular mechanisms of host manipulation, as well as in the genome evolution of manipulative parasites. The evidence of HGT between multicellular eukaryotes remains scarce but is increasing and, therefore, elucidating its mechanisms will advance our understanding of the enduring influence of HGT on the evolution of the web of life.

Rampant loss of universal metazoan genes revealed by a chromosome-level genome assembly of the parasitic Nematomorpha

Parasites may manipulate host behavior to increase the odds of transmission or to reach the proper environment to complete their life cycle.1,2 Members of the phylum Nematomorpha (known as horsehair worms, hairworms, or Gordian worms) are large endoparasites that affect the behavior of their arthropod hosts. In terrestrial hosts, they cause erratic movements toward bodies of water,3,4,5,6 where the adult worm emerges from the host to find mates for reproduction. We present a chromosome-level genome assembly for the freshwater Acutogordius australiensis and a draft assembly for one of the few known marine species, Nectonema munidae. The assemblies span 201 Mbp and 213 Mbp in length (N50: 38 Mbp and 716 Kbp), respectively, and reveal four chromosomes in Acutogordius, which are largely rearranged compared to the inferred ancestral condition in animals. Both nematomorph genomes have a relatively low number of genes (11,114 and 8,717, respectively) and lack a high proportion (∼30%) of universal single-copy metazoan orthologs (BUSCO genes7). We demonstrate that missing genes are not an artifact of the assembly process, with the majority of missing orthologs being shared by the two independent assemblies. Missing BUSCOs are enriched for Gene Ontology (GO) terms associated with the organization of cilia and cell projections in other animals. We show that most cilium-related genes conserved across eukaryotes have been lost in Nematomorpha, providing a molecular basis for the suspected absence of ciliary structures in these animals.

Extended epiphenotypes: Integrating epigenotypes into host behavioural manipulation by parasites

Abstract Biologists have long known that environmental context can create diverse phenotypes from identical genotypes. Thus, cells of the same foetus can grow into various organs depending on the molecular environment. Also, animals of the same genetic heritage can show different behaviours in different environments. Conrad Hal Waddington conceptualized epigenotypes in the 1930s, whereby modifications of genetic material could generate alternative modules of development arising out of nonvariant genetic information. His concept paved the way for a neo‐Darwinian synthesis by creating bidirectionality between the environment and genes. In a completely independent intellectual universe, Richard Dawkins introduced the idea of extended phenotype in the early 1980s. The hypothesis posits that the appropriate phenotype of genetic information is not limited to the organism but can ‘extend’ beyond the environment. Parasite manipulation of host behaviour presents a dramatic example of such extended phenotypes. In this perspective, we propose a synthesis between the earlier concept of epigenotypes and the later idea of extended phenotypes, namely a novel concept of extended epiphenotypes.Read the free Plain Language Summary for this article on the Journal blog.

The Biology and Ecology of Parasitoid Wasps of Predatory Arthropods.

Parasitoid wasps are important components of insect food chains and have played a central role in biological control programs for over a century. Although the vast majority of parasitoids exploit insect herbivores as hosts, others parasitize predatory insects and arthropods, such as ladybird beetles, hoverflies, lacewings, ground beetles, and spiders, or are hyperparasitoids. Much of the research on the biology and ecology of parasitoids of predators has focused on ladybird beetles, whose parasitoids may interfere with the control of insect pests like aphids by reducing ladybird abundance. Alternatively, parasitoids of the invasive ladybird Harmonia axyridis may reduce its harmful impact on native ladybird populations. Different life stages of predatory insects and spiders are susceptible to parasitism to different degrees. Many parasitoids of predators exhibit intricate physiological interrelationships with their hosts, adaptively manipulating host behavior, biology, and ecology in ways that increase parasitoid survival and fitness.

Dividing up the bill: Interactions between how parasitoids manipulate host behaviour and who pays the cost

Abstract Controlling host behaviour can be costly for parasites. In some parasitic systems, such as insect parasitoids, this physiological cost can be paid for by the mother parasite, her offspring or both. Parasitoid wasps provide examples of how individual parasites in a host–parasite system can vary in their opportunity, means and motive (i.e. fitness benefits) for manipulating host behaviour. Changes in host behaviour that occur very soon after infection are typically paid for by the mother parasitoid. She has the greatest opportunity (offspring are often still eggs), the means (neuroactive venoms) and benefits by promoting her offspring's success. Changes in host behaviour that occur late in the development of the offspring (e.g. host bodyguard behaviour) often hinge on some behaviour of the offspring (e.g. the exiting of the host). In these cases, the cost is paid largely by the offspring. The offspring have the greater opportunity, the means (e.g. secreting compounds into the host) and directly benefit by their increased survival. Gene delivery agents, such as symbiotic viruses, allow a reduction in the direct cost of parasitic manipulation to the parasite because the host is induced to use its own resources to produce the compounds needed to alter its behaviour. However, this method leads to indirect costs that are paid for by the offspring, due to a reduction in the host's resources that are available for their own growth. In gregarious systems, the possibility of cheating among the offspring (i.e. some individuals paying less than others to alter host behaviour) may select for modes of control that make cheating difficult. Determining who pays the physiological cost of manipulating host behaviour, and why, promises exciting insights into the evolution of parasitic manipulation in these systems. Read the free Plain Language Summary for this article on the Journal blog.

Baculoviruses hijack the visual perception of their caterpillar hosts to induce climbing behaviour thus promoting virus dispersal.

Baculoviruses can induce climbing behaviour in their caterpillar hosts to ensure they die at elevated positions to enhance virus transmission, providing an excellent model to study parasitic manipulation of host behaviour. Here, we demonstrate that climbing behaviour occurred mostly during daylight hours, and that the height at death of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV)-infected larvae increases with the height of the light source. Phototaxic and electroretinogram (ERG) responses were enhanced after HearNPV-infection in host larvae, and ablation of stemmata in infected larvae prevented both phototaxis and climbing behaviour. Through transcriptome and quantitative PCR, we confirmed that two opsin genes (a blue light-sensitive gene, HaBL; and a long wave-sensitive gene, HaLW) as well as the TRPL (transient receptor potential-like channel protein) gene, all integral to the host's visual perception pathway, were significantly upregulated after HearNPV infection. Knockout of HaBL, HaLW, or TRPL genes using the CRISPR/Cas9 system resulted in significantly reduced ERG responses, phototaxis, and climbing behaviour in HearNPV-infected larvae. These results reveal that HearNPV alters the expression of specific genes to hijack host visual perception at fundamental levels-photoreception and phototransduction-in order to induce climbing behaviour in host larvae.

Host Manipulation Mechanisms of SARS-CoV-2.

Viruses are the simplest of pathogens, but possess sophisticated molecular mechanisms to manipulate host behavior, frequently utilizing molecular mimicry. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to bind to the host receptor neuropilin-1 in order to gain entry into the cell. To do this, the virus utilizes its spike protein polybasic cleavage site (PCS), which mimics the CendR motif of neuropilin-1’s endogenous ligands. In addition to facilitating cell entry, binding to neuropilin-1 has analgesic effects. We discuss the potential impact of neuropilin-1 binding by SARS-CoV-2 in ameliorating sickness behavior of the host, and identify a convergent evolutionary strategy of PCS cleavage and subsequent neuropilin binding in other human viruses. In addition, we discuss the evolutionary leap of the ancestor of SARS-COV-2, which involved acquisition of the PCS thus faciliting binding to the neuropilin-1 receptor. Acquisition of the PCS by the ancestor of SARS-CoV-2 appears to have led to pleiotropic beneficial effects including enhancement of cell entry via binding to ACE2, facilitation of cell entry via binding to neuropilin-1, promotion of analgesia, and potentially the formation of decoy epitopes via enhanced shedding of the S1 subunit. Lastly, other potential neuromanipulation strategies employed by SARS-CoV-2 are discussed, including interferon suppression and the resulting reduction in sickness behavior, enhanced transmission through neurally mediated cough induction, and reduction in sense of smell.

Ophiocordyceps : Fungi Entomopatogen Penyebab Zombie Pada Serangga

Ophiocordyceps is special type of entomopathogenic fungi which well known to infect insects and turning them into zombie. A total of 250 species have been described from its genus, and some are known to control their hosts, which are most notably ants. They are ubiquitous within tropical rain forests across the board, with few publication reports from temperate ecosystems. These fungal pathogens possess the capacity to manipulate host behaviour in order to increase their own fitness. These entomopathogenic fungi cause their hosts frezee to die in an exposed area on the abaxial surface of leaves or branches, which then enhancing the fungus spore production and dispersal. Despite the high diversity of fungi and insect with vast tropical forest as well as drugs potency from Ophiocordyceps, publication of Ophiocordyces was rarely reported from Indonesia. This review will explain the evolution of Ophiocordyceps-insect interaction, simbiont distribution, and zombie-insect formation mechanism, in order to induce zombie-insect research in Indonesia.

Neofunctionalization of an ancient domain allows parasites to avoid intraspecific competition by manipulating host behaviour

Intraspecific competition is a major force in mediating population dynamics, fuelling adaptation, and potentially leading to evolutionary diversification. Among the evolutionary arms races between parasites, one of the most fundamental and intriguing behavioural adaptations and counter-adaptations are superparasitism and superparasitism avoidance. However, the underlying mechanisms and ecological contexts of these phenomena remain underexplored. Here, we apply the Drosophila parasite Leptopilina boulardi as a study system and find that this solitary endoparasitic wasp provokes a host escape response for superparasitism avoidance. We combine multi-omics and in vivo functional studies to characterize a small set of RhoGAP domain-containing genes that mediate the parasite’s manipulation of host escape behaviour by inducing reactive oxygen species in the host central nervous system. We further uncover an evolutionary scenario in which neofunctionalization and specialization gave rise to the novel role of RhoGAP domain in avoiding superparasitism, with an ancestral origin prior to the divergence between Leptopilina specialist and generalist species. Our study suggests that superparasitism avoidance is adaptive for a parasite and adds to our understanding of how the molecular manipulation of host behaviour has evolved in this system.

Zombie-ant fungi cross continents: II. Myrmecophilous hymenostilboid species and a novel zombie lineage

ABSTRACT Ophiocordyceps species infecting ants are globally distributed, with diversity concentrated in the tropics and decreasing with increasing latitude. Among these myrmecophilous species, the ones exhibiting the ability to manipulate host behavior, the so-called “zombie-ant fungi” of the O. unilateralis clade, have been studied progressively over the last decade. However, we know very little about other myrmecophilous groups, such as species within the Ophiocordyceps subgenus Neocordyceps. Species within this group exhibit Hymenostilbe asexual morphs with the ascospores readily breaking into part-spores and regularly kill their hosts on the forest floor, with few records of behavioral manipulation. Here, we describe five new species of Ophiocordyceps belonging to the subgenus Neocordyceps infecting ants in the rainforests of the Brazilian Amazon and Ghana and analyze their ability to manipulate host behavior. We also propose a new status for a species previously described as a variety, providing its phylogenetic placement for the first time. The species proposed herein can readily be separated using classic taxonomic criteria, and this is further supported by ecological and molecular multiloci data.

High-resolution analysis of baculovirus-induced host manipulation in the domestic silkworm, Bombyx mori.

Many parasites manipulate host behaviour to enhance their transmission. Baculoviruses induce enhanced locomotory activity (ELA) combined with subsequent climbing behaviour in lepidopteran larvae, which facilitates viral dispersal. However, the mechanisms underlying host manipulation system are largely unknown. Previously, larval locomotion during ELA was summarized as the distance travelled for a few minutes at several time points, which are unlikely to characterize ELA precisely, as ELA typically persists for several hours. In this study, we modified a recently developed method using time-lapse recording to characterize locomotion of Bombyx mori larvae infected with Bombyx mori nucleopolyhedrovirus (BmNPV) for 24 h at 3 s resolution. Our data showed that the locomotion of the mock-infected larvae was restricted to a small area, whereas the BmNPV-infected larvae exhibited a large locomotory area. These results indicate that BmNPV dysregulates the locomotory pattern of host larvae. Furthermore, both the mock- and BmNPV-infected larvae showed periodic cycles of movement and stationary behavior with a similar frequency, suggesting the physiological mechanisms that induce locomotion are unaffected by BmNPV infection. In contrast, the BmNPV-infected larvae exhibited fast and long-lasting locomotion compared with mock-infected larvae, which indicates that locomotory speed and duration are manipulated by BmNPV.

Risk-taking behaviour in African killifish – a case of parasitic manipulation?

Parasites commonly manipulate host behaviour to increase transmission success between hosts. While most behavioural changes comprise slight alterations to host activity patterns and habitat use, some represent impressive alterations to routine behaviour which, while having direct positive effects on parasite transmission, compromise host survival. Here, we report conspicuous risky behaviour in an African annual killifish, Nothobranchius furzeri, infected by metacercariae of a strigeid trematode, Apatemon sp., residing in their cranial cavity. We demonstrate a striking contrast in the spatial and temporal behavioural responses of fish from populations naturally infected with Apatemon sp. and fish from two control populations with either a similar baseline parasite fauna but lacking Apatemon, or an overall low-level of infection. During routine activity, fish from Apatemon-infected populations positioned themselves just below the water surface, while other fish spent most of their time near the bottom. During a simulated avian attack, killifish from Apatemon-infected populations jumped above the water surface, moved in an uncoordinated manner, and rotated in the upper water layer, while fish from the control populations rapidly escaped into deeper water and ceased moving. The same self-exposing behaviour (jumping out of the water and lying on floating lily pads for extended periods) was also observed under natural conditions. Such behaviour greatly facilitates location of Apatemon-infected host fish by avian definitive hosts, especially in turbid pools. Moreover, the nothobranchiid killifish host's own life history, i.e. an extremely short lifespan limited to several months, may represent an important driver in the evolution of behavioural manipulation.

Symbioses among ants and microbes.

Ants have been shown to engage in symbiosis across the tree of life, although our knowledge is far from complete. These interactions range from mutualistic to parasitic with several instances of manipulation of host behavior. Nutrient contributions in these symbioses include both farming for food and nitrogen recycling by gut-associated microbes. Interestingly, the ants that are mostly likely to host diverse and likely functional gut microbial communities are those that feed on extreme diets. Although we do see many instances of symbiosis between ants and microbes, there are also examples of species without a functional gut microbiome. Symbiosis among microbes and eukaryotic hosts is common and often considered a hallmark of multicellular evolution [1]. This is true among many of the over 13000 species of ants, although symbiosis between ants and microbes are not ubiquitous. These microbial-ant symbiotic interactions span the tree of life and include microbial eukaryotes, fungi, viruses, and bacteria. These interactions range from pathogenic to mutualistic, with many relationships still not well understood. Although our knowledge of the diversity of these microbes in ants is growing rapidly, and in some cases we know the function and interaction with the host, we still have much to learn about - the little things that run the little things that run the world!

Are Fungal Pathogens Manipulating Human Behavior?

Many pathogens, especially fungi, have evolved the capacity to manipulate host behavior, usually to improve their chances of spreading to other hosts. Such manipulation is difficult to observe in long-lived hosts, like humans. First, much time may separate cause from effect in the case of an infection that develops over a human life span. Second, the host-pathogen relationship may initially be commensal: the host becomes a vector for infection of other humans, and in exchange the pathogen remains discreet and does as little harm as possible. Commensalism breaks down with increasing age because the host is no longer a useful vector, being less socially active and at higher risk of death. Certain neurodegenerative diseases may therefore be the terminal stage of a longer-lasting relationship in which the host helps the pathogen infect other hosts, largely via sexual relations. Strains from the Candida genus are particularly suspect. Such pathogens seem to have co-evolved not only with their host population but also with the local social environment. Different social environments may have thus favored different pathogenic strategies for manipulation of human behavior.

Specialist and Generalist Fungal Parasites Induce Distinct Biochemical Changes in the Mandible Muscles of Their Host.

Some parasites have evolved the ability to adaptively manipulate host behavior. One notable example is the fungus Ophiocordyceps unilateralis sensu lato, which has evolved the ability to alter the behavior of ants in ways that enable fungal transmission and lifecycle completion. Because host mandibles are affected by the fungi, we focused on understanding changes in the metabolites of muscles during behavioral modification. We used High-Performance Liquid Chromatography-Mass/Mass (HPLC-MS/MS) to detect the metabolite difference between controls and O. unilateralis-infected ants. There was a significant difference between the global metabolome of O. unilateralis-infected ants and healthy ants, while there was no significant difference between the Beauveria bassiana treatment ants group compared to the healthy ants. A total of 31 and 16 of metabolites were putatively identified from comparisons of healthy ants with O. unilateralis-infected ants and comparisons of B. bassiana with O. unilateralis-infected samples, respectively. This result indicates that the concentrations of sugars, purines, ergothioneine, and hypoxanthine were significantly increased in O. unilateralis-infected ants in comparison to healthy ants and B. bassiana-infected ants. This study provides a comprehensive metabolic approach for understanding the interactions, at the level of host muscles, between healthy ants and fungal parasites.

Invisible Designers: Brain Evolution Through the Lens of Parasite Manipulation

AbstractThe ability of parasites to manipulate host behavior to their advantage has been studied extensively, but the impact of parasite manipulation on the evolution of neural and endocrine mechan...