Transcriptome ofSphaerospora molnari(Cnidaria, Myxosporea) blood stages provides proteolytic arsenal as potential therapeutic targets against sphaerosporosis in common carp

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F20%3A00537480" target="_blank" >RIV/60077344:_____/20:00537480 - isvavai.cz</a>

Výsledek na webu

<a href="https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-020-6705-y" target="_blank" >https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-020-6705-y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12864-020-6705-y" target="_blank" >10.1186/s12864-020-6705-y</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Transcriptome ofSphaerospora molnari(Cnidaria, Myxosporea) blood stages provides proteolytic arsenal as potential therapeutic targets against sphaerosporosis in common carp

Popis výsledku v původním jazyce

Background Parasites employ proteases to evade host immune systems, feed and replicate and are often the target of anti-parasite strategies to disrupt these interactions. Myxozoans are obligate cnidarian parasites, alternating between invertebrate and fish hosts. Their genes are highly divergent from other metazoans, and available genomic and transcriptomic datasets are limited. Some myxozoans are important aquaculture pathogens such asSphaerospora molnarireplicating in the blood of farmed carp before reaching the gills for sporogenesis and transmission. Proliferative stages cause a massive systemic lymphocyte response and the disruption of the gill epithelia by spore-forming stages leads to respiratory problems and mortalities. In the absence of aS. molnarigenome, we utilized a de novo approach to assemble the first transcriptome of proliferative myxozoan stages to identifyS. molnariproteases that are upregulated during the first stages of infection when the parasite multiplies massively, rather than in late spore-forming plasmodia. Furthermore, a subset of orthologs was used to characterize 3D structures and putative druggable targets. Results An assembled and host filtered transcriptome containing 9436 proteins, mapping to 29,560 contigs was mined for protease virulence factors and revealed that cysteine proteases were most common (38%), at a higher percentage than other myxozoans or cnidarians (25-30%). Two cathepsin Ls that were found upregulated in spore-forming stages with a presenilin like aspartic protease and a dipeptidyl peptidase. We also identified downregulated proteases in the spore-forming development when compared with proliferative stages including an astacin metallopeptidase and lipases (qPCR). In total, 235 transcripts were identified as putative proteases using a MEROPS database. In silico analysis of highly transcribed cathepsins revealed potential drug targets within this data set that should be prioritised for development. Conclusions In silico surveys for proteins are essential in drug discovery and understanding host-parasite interactions in non-model systems. The present study ofS. molnari's protease arsenal reveals previously unknown proteases potentially used for host exploitation and immune evasion. The pioneering dataset serves as a model for myxozoan virulence research, which is of particular importance as myxozoan diseases have recently been shown to emerge and expand geographically, due to climate change.

Název v anglickém jazyce

Transcriptome ofSphaerospora molnari(Cnidaria, Myxosporea) blood stages provides proteolytic arsenal as potential therapeutic targets against sphaerosporosis in common carp

Popis výsledku anglicky

Background Parasites employ proteases to evade host immune systems, feed and replicate and are often the target of anti-parasite strategies to disrupt these interactions. Myxozoans are obligate cnidarian parasites, alternating between invertebrate and fish hosts. Their genes are highly divergent from other metazoans, and available genomic and transcriptomic datasets are limited. Some myxozoans are important aquaculture pathogens such asSphaerospora molnarireplicating in the blood of farmed carp before reaching the gills for sporogenesis and transmission. Proliferative stages cause a massive systemic lymphocyte response and the disruption of the gill epithelia by spore-forming stages leads to respiratory problems and mortalities. In the absence of aS. molnarigenome, we utilized a de novo approach to assemble the first transcriptome of proliferative myxozoan stages to identifyS. molnariproteases that are upregulated during the first stages of infection when the parasite multiplies massively, rather than in late spore-forming plasmodia. Furthermore, a subset of orthologs was used to characterize 3D structures and putative druggable targets. Results An assembled and host filtered transcriptome containing 9436 proteins, mapping to 29,560 contigs was mined for protease virulence factors and revealed that cysteine proteases were most common (38%), at a higher percentage than other myxozoans or cnidarians (25-30%). Two cathepsin Ls that were found upregulated in spore-forming stages with a presenilin like aspartic protease and a dipeptidyl peptidase. We also identified downregulated proteases in the spore-forming development when compared with proliferative stages including an astacin metallopeptidase and lipases (qPCR). In total, 235 transcripts were identified as putative proteases using a MEROPS database. In silico analysis of highly transcribed cathepsins revealed potential drug targets within this data set that should be prioritised for development. Conclusions In silico surveys for proteins are essential in drug discovery and understanding host-parasite interactions in non-model systems. The present study ofS. molnari's protease arsenal reveals previously unknown proteases potentially used for host exploitation and immune evasion. The pioneering dataset serves as a model for myxozoan virulence research, which is of particular importance as myxozoan diseases have recently been shown to emerge and expand geographically, due to climate change.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology

Projekt

<a href="/cs/project/GX19-28399X" target="_blank" >GX19-28399X: AQUAPARA-OMICS: paraziti vodních organismů ve světě „biomiky“ – klíčové biologické otázky ve světle nových dat a moderních analytických nástrojů</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

BMC Genomics

ISSN

1471-2164

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

404

Kód UT WoS článku

000546752800001

EID výsledku v databázi Scopus

2-s2.0-85086686255