Host Use Research Articles

Host Manipulations Within Mutualisms: Role of Plant Hormones in Selective Resource Allocation.

In some mutualisms involving host plants, photoassimilates are provided as rewards to symbionts. Endophagous organisms often manipulate host plants to increase access to photoassimilates. Host manipulations by endophagous organisms that are also mutualists are poorly understood. We show host plant manipulations by symbionts and the role of phytohormones, i.e. the auxin indole-3-acetic acid (IAA), and the cytokinin trans-zeatin (tZ), in the brood-site pollination mutualism between fig trees and pollinator fig wasps. In this interaction, pollinator wasps pollinate Ficus flowers within an enclosed inflorescence called a syconium, in exchange for flowers that develop into galls nourishing pollinator offspring. To examine host manipulation by pollinator galls by affecting host fitness through seed reduction, we compared growth hormones released by syconial occupants within three experimentally produced treatment groups of syconia: S (containing only seeds), G (containing only pollinator galls) and SG (containing seeds and pollinator galls). We harvested syconia from each treatment in early and mid-phases of syconial maturation when maximal growth occurs and measured hormone levels. Hormones were reduced by mid-phase in general; however, their levels were mostly sustained in G syconia in the mid-phase, suggesting that galls manipulate the host to continuously access resources. We found no difference in IAA and tZ levels of S and G syconia. IAA concentrations were higher in SG syconia. From the perspective of the maintenance of mutualism, syconium volume and hormone concentrations were highest when both seeds and galls were present (SG treatment), indicating that both partners control allocation of resources to syconia.

On multiple infections by parasites with complex life cycles

Host manipulation is a common strategy of parasites with complex life cycles. It directly affects predator–prey dynamics in trophically transmitted parasites. Theoretical studies suggest that predation‐enhancing manipulation often decimates the prey population, making parasites prone to extinction. Host manipulation, however, can also reduce predation due to conflicting interests when multiple parasites infect a host, which is often neglected in theoretical studies. Misaligned interests of coinfecting parasites can occur due to limited carrying capacity or parasitoid developmental stage. Including this realistic complexity in a mathematical model, the results depart from previous studies substantially. We show that coinfecting multi‐trophic parasites can preserve the predator–prey system and themselves through manipulation and reproduction parameters. Our study highlights the necessity of and provides the means for incorporating the reality of multiple parasites and their multi‐trophic life cycles into the theory of parasite ecology.

Parasite-Driven host manipulation: The case of trematodes in Neotropical tadpoles

Parasites can impact tadpole survival in both lethal and sublethal ways. Sublethal effects include alterations in morphology and behavior, reduced competitive ability, and increased vulnerability to predation, while lethal effects result in direct mortality. These impacts can have significant consequences at both individual and population levels, especially given that amphibians host various parasites and pathogens, which may contribute to population declines. This study investigated the influence of digenetic trematodes, specifically Lophosicyadiplostomum sp. and Echinostomatidae metacercariae – larval stages found in second intermediate hosts, on the development and behavior of Physalaemus cuvieri tadpoles. Behavioral experiments assessed tadpole activity (time and movement number), water column use, and food consumption rates using video recordings and image analysis. Swimming performance was evaluated through predation simulations, and tadpole morphology (i.e. body size and mass) was measured post-experimentally. Infections by these digenetic trematodes resulted in a notable reduction in tadpole activity. A negative correlation was observed between Lophosicyadiplostomum sp. parasite load and both tadpole activity duration and movement frequency, indicating a common response to trematode infection. This study underscores the need for further research on digenetic trematodes to determine whether these behavioral modifications represent host manipulation by the parasites, potentially optimizing their transmission to the final host.

Effect of Trematode Metacercarial Infection on Walking in Larval Salamanders in the Southern Appalachian Mountains, USA

According to the Host Manipulation Hypothesis, parasites modify the phenotype of their host to enhance host–host transmission and thereby increase fitness. Metacercarial infection of some amphibians changes host behavior, including locomotion, and thereby enhances predation by the definitive host. To further test this hypothesis, it is first necessary to determine whether a parasite actually modifies a host’s phenotype. In the southern Appalachian Mountains of the US, metacercariae of the trematode Metagonimoides oregonensis (Price, 1931) encyst in the musculature of its second intermediate host, the salamander Desmognathus amphileucus Bishop, 1941. Metacercarial infections of musculature in fish negatively affect host swimming performance. Therefore, we tested the hypothesis that infection by M. oregonensis affects walking in the aquatic larvae of D. amphileucus. We compared this mode of locomotion between infected and uninfected larvae by placing them in 1 m troughs of water and allowing them to wander freely until they stopped. Non-parametric (Kaplan–Meier) survival analysis determined that infected salamanders stopped significantly sooner than uninfected ones. Because infected salamanders move less, the presence of this parasite may contribute to genetic divergence in these salamanders by slowing dispersal and concomitant gene flow. Our results suggest that macroparasites can potentially modify a host’s behavior with biological consequences beyond enhancement of parasite transmission.

CrANKing up the infection: ankyrin domains in Rickettsiales and their role in host manipulation.

Intracellular bacteria use secreted effector proteins to modify host biology and facilitate infection. For many of these microbes, a particular eukaryotic domain-the ankyrin repeat (ANK)-plays a central role in specifying the host proteins and pathways targeted by the microbe. While we understand much of how some ANKs function in model organisms like Legionella and Coxiella, the understudied Rickettsiales species harbor many proteins with ANKs, some of which play critical roles during infection. This minireview is meant to organize and summarize the research progress made in understanding some of these Rickettsiales ANKs as well as document some of the techniques that have driven much of this progress.

An array of Zymoseptoria tritici effectors suppress plant immune responses.

Zymoseptoria tritici is the most economically significant fungal pathogen of wheat in Europe. However, despite the importance of this pathogen, the molecular interactions between pathogen and host during infection are not well understood. Herein, we describe the use of two libraries of cloned Z. tritici effectors that were screened to identify effector candidates with putative pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI)-suppressing activity. The effectors from each library were transiently expressed in Nicotiana benthamiana, and expressing leaves were treated with bacterial or fungal PAMPs to assess the effectors' ability to suppress reactive oxygen species (ROS) production. From these screens, numerous effectors were identified with PTI-suppressing activity. In addition, some effectors were able to suppress cell death responses induced by other Z. tritici secreted proteins. We used structural prediction tools to predict the putative structures of all of the Z. tritici effectors and used these predictions to examine whether there was enrichment of specific structural signatures among the PTI-suppressing effectors. From among the libraries, multiple members of the killer protein-like 4 (KP4) and killer protein-like 6 (KP6) effector families were identified as PTI suppressors. This observation is intriguing, as these protein families were previously associated with antimicrobial activity rather than virulence or host manipulation. This data provides mechanistic insight into immune suppression by Z. tritici during infection and suggests that, similar to biotrophic pathogens, this fungus relies on a battery of secreted effectors to suppress host immunity during early phases of colonization.

Molecular Dialogue During Host Manipulation by the Vascular Wilt Fungus Fusarium oxysporum.

Vascular wilt fungi are a group of hemibiotrophic phytopathogens that infect diverse crop plants. These pathogens have adapted to thrive in the nutrient-deprived niche of the plant xylem. Identification and functional characterization of effectors and their role in the establishment of compatibility across multiple hosts, suppression of plant defense, host reprogramming, and interaction with surrounding microbes have been studied mainly in model vascular wilt pathogens Fusarium oxysporum and Verticillium dahliae. Comparative analysis of genomes from fungal isolates has accelerated our understanding of genome compartmentalization and its role in effector evolution. Also, advances in recent years have shed light on the cross talk of root-infecting fungi across multiple scales from the cellular to the ecosystem level, covering their interaction with the plant microbiome as well as their interkingdom signaling. This review elaborates on our current understanding of the cross talk between vascular wilt fungi and the host plant, which eventually leads to a specialized lifestyle in the xylem. We particularly focus on recent findings in F. oxysporum, including multihost associations, and how they have contributed to understanding the biology of fungal adaptation to the xylem. In addition, we discuss emerging research areas and highlight open questions and future challenges.

Widespread Wolbachia infection is correlated with increased mtDNA diversity in native bees across the Fijian archipelago

Insects have a complex coevolutionary history with bacterial symbionts, among which Wolbachia pipientis stands out for its prevalence and role in reproductive manipulation. Wolbachia can induce cytoplasmic incompatibility, feminisation, male killing, and parthenogenesis, greatly influence the population genetics of their hosts and are potential drivers of invertebrate speciation. We might then assume that Wolbachia could act synergistically with other factors, such as niche conservation and isolation by distance, to drive speciation in hyper-diverse invertebrate taxa. The Fijian archipelago hosts a remarkable and recently diverged clade of Lasioglossum (Homalictus) bees. Some of these Lasioglossum have highly unusual species-level sex ratios and mitochondrial diversities, which can be hallmarks of infection by a bacterial reproductive manipulator. To examine the role of Wolbachia in Fijian Lasioglossum speciation, we screened the endemic Fijian bees for Wolbachia using the Wolbachia surface protein gene (wsp). We compare the distribution of Wolbachia infection across species with host mitochondrial haplotype diversity and conducted phylogenetic analyses to determine the relationship of host relatedness and symbiont infection status. We found that Wolbachia haplotypes probably span across supergroups A and B. In addition, we found multiple haplotypes were highly similar, with the most abundant group of wsp haplotypes being closely related with the drosophila Wolbachia strain wHa. We found evidence of mostly horizontal and limited vertical transmission, and little evidence for Wolbachia-host cospeciation. We show that, contrary to general patterns, Wolbachia-infected Lasioglossum species have higher mitochondrial diversity. Finally, we present evidence for the potential of multiple modes of host manipulation in this clade.

Microbial artists: the role of parasite microbiomes in explaining colour polymorphism among amphipods and potential link to host manipulation.

Parasite infections are increasingly reported to change the microbiome of the parasitised hosts, while parasites bring their own microbes to what can be a multi-dimensional interaction. For instance, a recent hypothesis suggests that the microbial communities harboured by parasites may play a role in the well-documented ability of many parasites to manipulate host phenotype, and explain why the degree to which host phenotype is altered varies among conspecific parasites. Here, we explored whether the microbiomes of both hosts and parasites are associated with variation in host manipulation by parasites. Using colour quantification methods applied to digital images, we investigated colour variation among uninfected Transorchestia serrulata amphipods, as well as amphipods infected with Plagiorhynchus allisonae acanthocephalans and with a dilepidid cestode. We then characterised the bacteriota of amphipod hosts and of their parasites, looking for correlations between host phenotype and the bacterial taxa associated with hosts and parasites. We found large variation in amphipod colours, and weak support for a direct impact of parasites on the colour of their hosts. Conversely, and most interestingly, the parasite's bacteriota was more strongly correlated with colour variation among their amphipod hosts, with potential impact of amphipod-associated bacteria as well. Some bacterial taxa found associated with amphipods and parasites may have the ability to synthesise pigments, and we propose they may interact with colour determination in the amphipods. This study provides correlational support for an association between the parasite's microbiome and the evolution of host manipulation by parasites and host-parasite interactions more generally.

Phenotyping and Molecular Characterization of Durable Resistance in Bread Wheat for Stripe Rust (Puccinia striiformis f.sp. tritici)

Stripe rust of wheat serious biotic stress to wheat aiming in the reduction of yield losses with biotrophic nature of the pathogen attacks mainly the foliage parts and makes it render for photosynthetic ability of the host. Host manipulation with genetic advancement one of the major steps in the breeding programme. The durability of the cultivar can be achieved with stacking of minor gene and their combinations with major R-gene The postulated gene identified diversified resistance patterns with various combination of APR and ASR gene under field conditions and the frequencies of the postulated genes as Yr16 (22.9%), Yr18 (59.0%), Yr29 (44.2%), Yr9 (47.5) and Yr2 (73.7%) respectively, Yr16 postulated germplasm shows strong field resistance at adult plant stage with disease response of R to RMR for Pst Pathotypes such as 78S84, 46S119, 110S119 and 238S119.

Rickettsia induces strong cytoplasmic incompatibility in a predatory insect.

Rickettsia, a group of intracellular bacteria found in eukaryotes, exhibits diverse lifestyles, with some acting as vertebrate pathogens transmitted by arthropod vectors and others serving as maternally transmitted arthropod endosymbionts, some of which manipulate host reproduction for their own benefit. Two phenotypes, namely male-killing and parthenogenesis induction are known as Rickettsia-induced host reproductive manipulations, but it remains unknown whether Rickettsia can induce other types of host manipulation. In this study, we discovered that Rickettsia induced strong cytoplasmic incompatibility (CI), in which uninfected females produce no offspring when mated with infected males, in the predatory insect Nesidiocoris tenuis (Hemiptera: Miridae). Molecular phylogenetic analysis revealed that the Rickettsia strain was related to Rickettsia bellii, a common insect endosymbiont. Notably, this strain carried plasmid-encoded homologues of the CI-inducing factors (namely cifA-like and cifB-like genes), typically found in Wolbachia, which are well-known CI-inducing endosymbionts. Protein domain prediction revealed that the cifB-like gene encodes PD-(D/E)XK nuclease and deubiquitinase domains, which are responsible for Wolbachia-induced CI, as well as ovarian tumour-like (OTU-like) cysteine protease and ankyrin repeat domains. These findings suggest that Rickettsia and Wolbachia endosymbionts share underlying mechanisms of CI and that CI-inducing ability was acquired by microbes through horizontal plasmid transfer.

Making shelter for enemies: parasitoid-induced shelter-building behaviour in Paraponyx stagnalis

ABSTRACT Manipulative parasitoids manipulate the behaviour of their hosts in such a way as to benefit their own offspring. Paraponyx stagnalis Zeller is a leaf case worm caterpillar pest of rice and pupates in cases made out of cut leaf blades. These shelters are typically open-ended tubular cases. Its solitary primary endoparasitoid – Apanteles sp. – triggers changes in the way it sews the cases. The observed changes in the folded leaf shelter may serve various functions for the developing parasitoid, such as minimising the risk of hyperparasitism and predation, and enhancing structural stability. To obtain evidence to support these hypotheses, we (1) documented the morphotype of the cases/puparia constructed by unparasitised and parasitised P. stagnalis larval instars, (2) studied the overall rate of primary parasitism of P. stagnalis by Apanteles sp. and (3) studied the rate of hyperparasitism of primary parasitoids in 10 rice fields of south India. Unlike the unparasitised third-instar host larvae, the parasitised larvae sealed the open ends of the folded leaf shelter with silken threads, affixed the puparium to rice leaves and made small cases. The overall parasitism rate was about 40%. However, the hyperparasitism was between 0.6 and 1%. Though the primary parasitism by Apanteles sp. is considerably higher in all 10 fields, the meagre incidence of hyperparasitism strengthens our hypothesis that the modified puparium construction might be triggered by the primary parasitoid and beneficial for the offspring of the primary parasitoid. Our field observations suggest that future experimental studies can bring mechanical evidence for host manipulation by Apanteles sp.

Glyphosate-environmental variables interaction: How does it affect the parasite Chordodes nobilii?

The worldwide used herbicide Glyphosate can interact with environmental variables, but there is limited information on the influence of environmental stressors on its toxicity. Environmental changes could modify glyphosate effects on non-target organisms, including parasites such as gordiids. The freshwater microscopic larvae of the gordiid Chordodes nobilii are sensitive to several pollutants and environmental variables, but their combined effect has not been evaluated yet. The aim of this study was to evaluate the impact of temperature, pH and exposure time on the toxicity of Glyphosate to C. nobilii larvae. A protocol was followed to evaluate the infectivity of larvae treated with factorial combinations of concentration (0 and 0.067 mg/L), exposure time (24 and 48 h), temperature (18, 23 and 28 °C), and pH (7, 8 and 9). The reference values were 23 °C, pH 8 and 48 h. The interaction effect on the infectivity of gordiid larvae was assessed post-exposure using Aedes aegyptii larvae as host. Results were evaluated using GLMM, which does not require data transformation. The modeling results revealed three highly significant triple interactions. Glyphosate toxicity varied depending on the combination of variables, with a decrease being observed after 24 h-exposure at pH 7 and 23 °C. Glyphosate and 28 °C combination led to slightly reduced infectivity compared to temperature alone. This study is the first to report the combined effects of glyphosate, temperature, pH and time on a freshwater animal. It demonstrates that a specific combination of factors determines the effect of glyphosate on a non-target organism. The potential use of C. nobilli as a bioindicator is discussed. In the context of global warming and considering that the behavioral manipulation of terrestrial hosts by gordiids can shape community structure and the energy flow through food webs, our results raise concerns about possible negative effects of climate change on host-parasite dynamics.

Complex effects of testosterone level on ectoparasite load in a ground squirrel: an experimental test for the immunocompetence handicap hypothesis

BackgroundThe immunocompetence handicap hypothesis suggests that males with a higher testosterone level should be better at developing male secondary traits, but at a cost of suppressed immune performance. As a result, we should expect that males with an increased testosterone level also possess a higher parasite load. However, previous empirical studies aimed to test this prediction have generated mixed results. Meanwhile, the effect of testosterone level on parasite load in female hosts remains poorly known.MethodsIn this study, we tested this prediction by manipulating testosterone level in Daurian ground squirrels (Spermophilus dauricus), a medium-sized rodent widely distributed in northeast Asia. S. dauricus is an important host of ticks and fleas and often viewed as a considerable reservoir of plague. Live-trapped S. dauricus were injected with either tea oil (control group) or testosterone (treatment group) and then released. A total of 10 days later, the rodents were recaptured and checked for ectoparasites. Fecal samples were also collected to measure testosterone level of each individual.ResultsWe found that testosterone manipulation and sex of hosts interacted to affect tick load. At the end of the experiment, male squirrels subjected to testosterone implantation had an averagely higher tick load than males from the control group. However, this pattern was not found in females. Moreover, testosterone manipulation did not significantly affect flea load in S. dauricus.ConclusionsOur results only lent limited support for the immunocompetence handicap hypothesis, suggesting that the role of testosterone on regulating parasite load is relatively complex, and may largely depend on parasite type and gender of hosts.Graphical

Response of Hypothenemus hampei Ferrari (Coleoptera: Curculionidae: Scolytinae) parasitized by the nematode Metaparasitylenchus hypothenemi Poinar (Tylenchida: Allantonematidae) to different colors of light.

Metaparasitylenchus hypothenemi is a nematode that naturally parasitizes Hypothenemus hampei in a coffee-producing region in Chiapas, Mexico. This study investigated changes in the attraction of parasitized borers to light. We compared the attraction of adult H. hampei females (parasitized and uninfected) to 14 different light wavelengths (350-670 nm) with a control (570 nm, yellow) under laboratory conditions. The response ranges of non-parasitized and parasitized borers were 370-650 nm and 340-650 nm, respectively. The attraction curve showed a similar shape in both borer groups (parasitized and non-parasitized), but a wide wavelength range (380-590 nm) attracted more parasitized than non-parasitized borers. The maximum response of the uninfected borers occurred at 520 nm (green), while parasitized borers exhibited three response peaks (380 nm, violet; 460 nm, blue; 520 nm, green). Parasitized borers were significantly more attracted to green light (520 nm) than to the control. The altered attraction to light in borers parasitized by M. hypothenemi is discussed from the perspective of possible host manipulation and the natural prevalence of this parasite.

The WY Domain of an RxLr Effector Drives Interactions with a Host Target Phosphatase to Mimic Host Regulatory Proteins and Promote Phytophthora infestans Infection.

Plant pathogens manipulate the cellular environment of the host to facilitate infection and colonization that often lead to plant diseases. To accomplish this, many specialized pathogens secrete virulence proteins called effectors into the host cell, which subvert processes such as immune signaling, gene transcription, and host metabolism. Phytophthora infestans, the causative agent of potato late blight, employs an expanded repertoire of RxLR effectors with WY domains to manipulate the host through direct interaction with protein targets. However, our understanding of the molecular mechanisms underlying the interactions between WY effectors and their host targets remains limited. In this study, we performed a structural and biophysical characterization of the P. infestans WY effector Pi04314 in complex with the potato Protein Phosphatase 1-c (PP1c). We elucidate how Pi04314 uses a WY domain and a specialized C-terminal loop carrying a KVxF motif that interact with conserved surfaces on PP1c, known to be used by host regulatory proteins for guiding function. Through biophysical and in planta analyses, we demonstrate that Pi04314 WY or KVxF mutants lose their ability to bind PP1c. The loss of PP1c binding correlates with changes in PP1c nucleolar localization and a decrease in lesion size in plant infection assays. This study provides insights into the manipulation of plant hosts by pathogens, revealing how effectors exploit key regulatory interfaces in host proteins to modify their function and facilitate disease. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Parasite evolution of host manipulation strategies with fluctuating ecological dynamics.

Trophically transmitted parasites often infect an intermediate prey host and manipulate their behaviour to make predation more likely, thus facilitating parasite transmission to the definitive host. However, it is unclear when such a manipulation strategy should be expected to evolve. We develop the first evolutionary invasion model to explore the evolution of manipulation strategies that are in a trade-off with parasite production of free-living spores. We find that the size of the susceptible prey population together with the threat of predation drives manipulation evolution. We find that it is only when the susceptible prey population is large and the threat of predation is relatively small that selection favours manipulation strategies over spore production. We also confirm that the system exhibits cyclic population dynamics, and this can influence the qualitative direction of selection.

Toxoplasma protein export and effector function.

Toxoplasma gondii is a single-celled eukaryotic parasite with a considerable host range that must invade the cells of warm-blooded hosts to survive and replicate. The challenges and opportunities that such a strategy represent have been met by the evolution of effectors that are delivered into host cells, counter host defences and co-opt host cell functions for their own purposes. These effectors are delivered in two waves using distinct machinery for each. In this Review, we focus on understanding the architecture of these protein-export systems and how their protein cargo is recognized and selected. We discuss the recent findings on the role that host manipulation has in latent Toxoplasma infections. We also discuss how these recent findings compare to protein export in the related Plasmodium spp. (the causative agent of malaria) and how this can inform our understanding of host manipulation in the larger Apicomplexa phylum and its evolution.

Crystal structure of bacterial ubiquitin ADP-ribosyltransferase CteC reveals a substrate-recruiting insertion

ADP-ribosylation is a post-translational modification involved in regulation of diverse cellular pathways. Interestingly, many pathogens have been identified to utilize ADP-ribosylation as a way for host manipulation. A recent study found that CteC, an effector from the bacterial pathogen Chromobacterium violaceum, hinders host ubiquitin signaling pathways via installing mono-ADP-ribosylation on threonine 66 of ubiquitin. However, the molecular basis of substrate recognition by CteC is not well-understood. In this paper, we probed the substrate specificity of this effector at protein and residue levels. We also determined the crystal structure of CteC in complex with NAD+, which revealed a canonical mono-ADP-ribosyltransferase fold with an additional insertion domain. The AlphaFold predicted model differed significantly from the experimentally determined structure, even in regions not used in crystal packing. Biochemical and biophysical studies indicated unique features of the NAD+ binding pocket, while showing selectivity distinction between ubiquitin and structurally close ubiquitin-like modifiers and the role of the insertion domain in substrate recognition. Together, this study provides insights into the enzymatic specificities and the key structural features of a novel bacterial ADP-ribosyltransferase involved in host-pathogen interaction.

Early divergent responses to virulent and attenuated vaccine isolates of Flavobacterium covae sp. nov. In channel catfish, Ictalurus punctatus

Columnaris disease continues to inflict substantial losses among freshwater cultured species since its first description one hundred years ago. The experimental and anecdotal evidence suggests an expanded range and rising virulence of columnaris worldwide due to the warming global climate. The channel catfish (Ictalurus punctatus) are particularly vulnerable to columnaris. A recently developed live attenuated vaccine (17–23) for Flavobacterium columnare (now Flavobacterium covae sp. nov.) demonstrated superior protection for vaccinated catfish against genetically diverse columnaris isolates. In this study, we aimed to elucidate the molecular mechanisms and patterns of immune evasion and host manipulation linked to virulence by comparing gene expression changes in the host after the challenge with a virulent (BGSF-27) or live attenuated F. covae sp. nov. vaccine (17–23). Thirty-day-old fry were accordingly challenged with either virulent or vaccine isolates. Gill tissues were collected at 0 h (control), 1 h, and 2 h post-infection, which are two critical time points in early host-pathogen interactions. Transcriptome profiling of the gill tissues revealed a larger number (518) of differentially expressed genes (DEGs) in vaccine-exposed fish than those exposed to the virulent pathogen (321). Pathway analyses suggested potent suppression of early host immune responses by the virulent isolate through a higher expression of nuclear receptor corepressors (NCoR) responsible for antagonizing macrophage and T-cell signaling. Conversely, in vaccinated fry, we observed induction of Ca2+/calmodulin-dependent protein kinase II (CAMKII), responsible for clearing NCoR, and commensurate up-regulation of transcription factor AP-1 subunits, c-Fos, and c-Jun. As in mammalian systems, AP-1 expression was connected with a broad immune activation in vaccinated fry, including induction of CC chemokines, proteinases, iNOS, and IL-12b. Relatedly, divergent expression patterns of Src tyrosine kinase Lck, CD44, and CD28 indicated a delay or suppression of T-cell adhesion and activation in fry exposed to the virulent isolate. Broader implications of these findings will be discussed. The transcriptomic differences between virulent and attenuated bacteria may offer insights into how the host responds to the vaccination or infection and provide valuable knowledge to understand the early immune mechanisms of columnaris disease in aquaculture.