Know your enemy – transcriptome of myxozoan<i>Tetracapsuloides bryosalmonae</i>reveals potential drug targets against proliferative kidney disease in salmonids

Ahmad, Freed; Debes, Paul V.; Pukk, Lilian; Kahar, Siim; Hartikainen, Hanna; Gross, Riho; Vasemägi, Anti

doi:10.1017/s003118202100010x

Cited by 12 publications

(20 citation statements)

References 94 publications

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“…In spite of the immune functions of the kidney, T. bryosalmonae can successfully undergo sporogony in the kidney of the affected fish and be released in the urine ( Sudhagar et al., 2019 ; Sudhagar et al., 2020 ) suggesting that this parasite has evolved to survive in an extremely hostile environment by molecular adaption. Most of the previous experiments on brown trout - T. bryosalmonae interactions were conducted to understand the host (brown trout) response ( Kumar et al., 2014 ; Kumar et al., 2015 ; Bailey et al., 2019 ; Sudhagar et al., 2019 ; Sudhagar et al., 2020 ; Shivam et al., 2021 ; Sudhagar et al., 2022 ), while only a few studies focused on generating molecular information on T. bryosalmonae ( Ahmad et al., 2021 ; Faber et al., 2021 ; Kumar et al., 2021 ). Identification of in vivo induced antigens or genes of the parasite during host-pathogen interactions, particularly during its development host, will provide valuable insight into the molecular adaption of the parasite.…”

Section: Discussionmentioning

confidence: 99%

Identification of in vivo induced antigens of the malacosporean parasite Tetracapsuloides bryosalmonae (Cnidaria) using in vivo induced antigen technology

Kumar

Sudhagar

Shivam

et al. 2022

Front. Cell. Infect. Microbiol.

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Tetracapsuloides bryosalmonae is a malacosporean endoparasite that causes proliferative kidney disease (PKD) in wild and farmed salmonids in Europe and North America. The life cycle of T. bryosalmonae completes between invertebrate bryozoan and vertebrate fish hosts. Inside the fish, virulence factors of T. bryosalmonae are induced during infection or interactions with host cells. T. bryosalmonae genes expressed in vivo are likely to be important in fish pathogenesis. Herein, we identify in vivo induced antigens of T. bryosalmonae during infection in brown trout (Salmo trutta) using in vivo induced antigen technology (IVIAT). Brown trout were exposed to the spores of T. bryosalmonae and were sampled at different time points. The pooled sera were first pre-adsorbed with antigens to remove false positive results. Subsequently, adsorbed sera were used to screen a T. bryosalmonae cDNA phage expression library. Immunoscreening analysis revealed 136 immunogenic T. bryosalmonae proteins induced in brown trout during parasite development. They are involved in signal transduction, transport, metabolism, ion-protein binding, protein folding, and also include hypothetical proteins, of so far unknown functions. The identified in vivo induced antigens will be useful in the understanding of T. bryosalmonae pathogenesis during infection in susceptible hosts. Some of the antigens found may have significant implications for the discovery of candidate molecules for the development of potential therapies and preventive measures against T. bryosalmonae in salmonids.

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Section: Discussionmentioning

confidence: 99%

Identification of in vivo induced antigens of the malacosporean parasite Tetracapsuloides bryosalmonae (Cnidaria) using in vivo induced antigen technology

Kumar

Sudhagar

Shivam

et al. 2022

Front. Cell. Infect. Microbiol.

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“…The patterns of expression observed for these cysteine proteases do not exclude the possibility that other cysteine proteases could have important roles in pathogenesis of genotype IIR. The protease repertoire of C. shasta includes other cysteine proteases (Table 2; Alama-Bermejo et al, 2020;Ahmad et al, 2021), which may contribute to the parasite's proteolytic activity on the host intestine extracellular matrix, as reported in other histolytical parasites e.g. Entamoeba histolytica (Kissoon-Singh et al, 2011), where cysteine proteases are primary virulence factors.…”

Section: The Less Virulent Genotype May Use Cysteine Proteases To Evade the Host Immune Systemmentioning

confidence: 97%

Proteases as Therapeutic Targets Against the Parasitic Cnidarian Ceratonova shasta: Characterization of Molecules Key to Parasite Virulence In Salmonid Hosts

Alama-Bermejo

Bartošová-Sojková

Holzer

2022

Front. Cell. Infect. Microbiol.

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Proteases and their inhibitors play critical roles in host-parasite interactions and in the outcomes of infections. Ceratonova shasta is a myxozoan pathogen that causes enteronecrosis in economically important salmonids from the Pacific Northwest of North America. This cnidarian parasite has host-specific genotypes with varying virulence, making it a powerful system to decipher virulence mechanisms in myxozoans. Using C. shasta genome and transcriptome, we identified four proteases of different catalytic types: cathepsin D (aspartic), cathepsin L and Z-like (cysteine) and aminopeptidase-N (metallo); and a stefin (cysteine protease inhibitor), which implied involvement in virulence and hence represent target molecules for the development of therapeutic strategies. We characterized, annotated and modelled their 3D protein structure using bioinformatics and computational tools. We quantified their expression in C. shasta genotype 0 (low virulence, no mortality) and IIR (high virulence and mortality) in rainbow trout Oncorhynchus mykiss, to demonstrate that there are major differences between the genotypes during infection and parasite development. High proliferation of genotype IIR was associated with high expression of the cathepsin D and the stefin, likely correlated with high nutrient demands and to regulate cell metabolism, with upregulation preceding massive proliferation and systemic dispersion. In contrast, upregulation of the cathepsin L and Z-like cysteine proteases may have roles in host immune evasion in genotype 0 infections, which are associated with low proliferation, low inflammation and non-destructive development. In contrast to the other proteases, C. shasta aminopeptidase-N appears to have a prominent role in nematocyst formation in both genotypes, but only during sporogenesis. Homology searches of C. shasta proteases against other myxozoan transcriptomes revealed a high abundance of cathepsin L and aminopeptidase homologs suggesting common gene requirements across species. Our study identified molecules of potential therapeutic significance for aquaculture and serves as a baseline for future research aimed at functional characterisation of these targets.

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“…On the host side, it seems reasonable to deduce that it would be beneficial to prevent the gross tissue damage that occurs with the massive granulomatous inflammation shown in advanced PKD. Recent progress in comparative transcriptomics (Ahmad, Debes, Pukk, et al., 2021; Faber et al., 2021) and genetic profiling of immunity (Bailey, Holland, et al., 2020) is now starting to reveal the extent to which such adaptations have evolved in both parasite and its hosts (Ahmad, Debes, Nousiainen, et al., 2021). In general, such adaptions are expected to result in evolution for low virulence of the parasitic infection and this would fit the hypothesis that proliferation of T. bryosalmonae in the kidney does not result in gross pathology at water temperature conditions that prevailed in salmonid habitat before anthropogenic global warming (Borgwardt et al., 2020; Bruneaux et al., 2017; Lauringson et al., 2021; Strepparava et al., 2018; Wahli et al., 2002).…”

Section: The Relation Between Temperature and Proliferative Kidney Di...mentioning

confidence: 99%

“…This situation might, however, change as recent transcriptome studies have identified promising molecular targets (i.e. endoglycoceramidase, legumain‐like protease, carbonic anhydrase 2 and pancreatic lipase‐related protein 2) that can be used for developing future drugs against T. bryosalmonae infections (Ahmad, Debes, Pukk, et al., 2021; Faber et al., 2021). The main solution for farms with mortalities related to PKD has been to raise the fingerlings using cool spring or mountain water (<15°C; De Kinkelin & Loriot, 2001).…”

Section: Management Options For Mitigating Pkd In Salmonidsmentioning

confidence: 99%

“…Trout with PKD have been shown to be sensitive to additional stressors like pollution (Bailey, Rubin, et al., 2018; El‐Matbouli & Hoffmann, 2002; Rubin et al., 2019) and respiratory distress (see Clifton‐Hadley et al., 1984). Furthermore, restricting the diet has been found to decrease mortality in PKD diseased trout (Ferguson & Ball, 1979), which might be related to a positive effect on water quality. Recent developments in transcriptomics greatly increase the possibilities to find specific physiological disease pathways that can be used in developing drugs and vaccines against PKD (Ahmad, Debes, Pukk, et al., 2021; Faber et al., 2019; Faber et al., 2021). Also, the route of treatment should be further developed as vaccination might be costly and impractical for production farms when the fish are fingerlings, still they could be very useful when protecting valuable brood stock against PKD in aquaculture or in the field. Setting up legal frameworks to control or monitor outbreaks of PKD will help to gather information on disease distribution, severity and impact.…”

Section: Management Options For Mitigating Pkd In Salmonidsmentioning

confidence: 99%

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Mitigating human impacts including climate change on proliferative kidney disease in salmonids of running waters

Ros

Schmidt‐Posthaus

Brinker

2022

Journal of Fish Diseases

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Over the last two decades, an increasing number of reports have identified a decline in salmonid populations, possibly linked to infection with the parasite Tetracapsuloides bryosalmonae and the corresponding disease, that is, proliferative kidney disease (PKD). The life cycle of this myxozoan parasite includes sessile bryozoan species as invertebrate host, which facilitates the distribution of the parasite in running waters. As the disease outcome is temperature dependent, the impact of the disease on salmonid populations is increasing with global warming due to climate change. The goal of this review is to provide a detailed overview of measures to mitigate the effects of PKD on salmonid populations. It first summarizes the parasite life cycle, temperature‐driven disease dynamics and new immunological and molecular research into disease resistance and, based on this, discusses management possibilities. Sophisticated management actions focusing on local adaptation of salmonid populations, restoration of the riverine ecosystem and keeping water temperatures cool are necessary to reduce the negative effects of PKD. Such actions include temporary stocking with PKD‐resistant salmonids, as this may assist in conserving current populations that fail to reproduce.

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Know your enemy – transcriptome of myxozoanTetracapsuloides bryosalmonaereveals potential drug targets against proliferative kidney disease in salmonids

Abstract: Abstract

Cited by 12 publications

References 94 publications

Identification of in vivo induced antigens of the malacosporean parasite Tetracapsuloides bryosalmonae (Cnidaria) using in vivo induced antigen technology

Identification of in vivo induced antigens of the malacosporean parasite Tetracapsuloides bryosalmonae (Cnidaria) using in vivo induced antigen technology

Proteases as Therapeutic Targets Against the Parasitic Cnidarian Ceratonova shasta: Characterization of Molecules Key to Parasite Virulence In Salmonid Hosts

Mitigating human impacts including climate change on proliferative kidney disease in salmonids of running waters

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