The Parasite Schistocephalus Solidus Secretes
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Berger et al. Parasites Vectors (2021) 14:436 https://doi.org/10.1186/s13071-021-04933-w Parasites & Vectors RESEARCH Open Access The parasite Schistocephalus solidus secretes proteins with putative host manipulation functions Chloé Suzanne Berger1,2,3, Jérôme Laroche2, Halim Maarouf2, Hélène Martin1,2,4, Kyung‑Mee Moon5, Christian R. Landry1,2,4,6,7, Leonard J. Foster5 and Nadia Aubin‑Horth1,2,3* Abstract Background: Manipulative parasites are thought to liberate molecules in their external environment, acting as manipulation factors with biological functions implicated in their host’s physiological and behavioural alterations. These manipulation factors are part of a complex mixture called the secretome. While the secretomes of various parasites have been described, there is very little data for a putative manipulative parasite. It is necessary to study the molecular interaction between a manipulative parasite and its host to better understand how such alterations evolve. Methods: Here, we used proteomics to characterize the secretome of a model cestode with a complex life cycle based on trophic transmission. We studied Schistocephalus solidus during the life stage in which behavioural changes take place in its obligatory intermediate fsh host, the threespine stickleback (Gasterosteus aculeatus). We produced a novel genome sequence and assembly of S. solidus to improve protein coding gene prediction and annotation for this parasite. We then described the whole worm’s proteome and its secretome during fsh host infection using LC–MS/MS. Results: A total of 2290 proteins were detected in the proteome of S. solidus, and 30 additional proteins were detected specifcally in the secretome. We found that the secretome contains proteases, proteins with neural and immune functions, as well as proteins involved in cell communication. We detected receptor‑type tyrosine‑protein phosphatases, which were reported in other parasitic systems to be manipulation factors. We also detected 12 S. solidus‑specifc proteins in the secretome that may play important roles in host–parasite interactions. Conclusions: Our results suggest that S. solidus liberates molecules with putative host manipulation functions in the host and that many of them are species‑specifc. Keywords: Schistocephalus solidus, Secretome, Proteomics, Manipulation factor, Parasite, Behaviour Background release manipulation factors that interfere with the host Parasites have major impacts on their hosts, including physiological and central nervous systems [5–7]. Tese on their morphology [1], physiology [2], and behaviour manipulation factors are thought to be part of a complex [3, 4]. To induce these complex changes in their hosts, mixture of molecules called the secretome, which is a key it has been proposed that parasites produce, store, and element of parasite–host interactions [6]. Te secretome of a parasite includes lipids [8], nucleic acids [9], and proteins [10], which are sometimes protected inside *Correspondence: Nadia.Aubin‑[email protected] extracellular vesicles [11]. Using molecular and bioinfor- 1 Département de Biologie, Université Laval, Quebec, QC, Canada matics approaches, the proteomic fraction of secretomes Full list of author information is available at the end of the article © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Berger et al. Parasites Vectors (2021) 14:436 Page 2 of 20 of parasites infecting humans [12] and livestock [13] have possible to infer a list of putative manipulation factors, been described, both in terms of protein composition which would target the neural and the immune systems and function [14, 15] (see Table 1 for a review). of the hosts and induce behavioural changes (Table 1). Te secretomes that have been examined so far are Our knowledge regarding if and how many proteins enriched in peptidases and proteases [12, 15], which are with neural and immune functions can be found in the known to weaken the host immunity barriers. Other secretomes of manipulative parasites is very limited, and secreted proteins, such as paramyosin in the blood fuke is based in many cases on inferred proteins rather than Schistosoma mansoni, have been shown to help the para- actual detection. site to escape the host immune response, while secreted One particularly powerful model to study behavioural proteins involved in calcium functions have impacts on manipulation is the cestode Schistocephalus solidus the host neural activity [12]. In the context of behavioural [27]. Tis parasite exhibits a complex life cycle based on manipulation, the secretome is a logical potential source trophic transmission that includes three hosts: a cope- of manipulation factors. However, the secretome con- pod, the threespine stickleback (Gasterosteus aculeatus, tent of a behaviour-manipulating parasite has rarely been obligatory intermediate fsh host), and a fsh-eating bird, investigated, to the point that secretomes are referred in which S. solidus reproduces [27, 28]. S. solidus infects to as “the missing link in parasite manipulation” [7]. the threespine stickleback’s abdominal cavity through Te literature contains several reports from which it is the ingestion of a parasitized copepod [29]. Te Table 1 Proteomic content (directly measured or inferred) of the secretomes of diferent parasite species Parasitic species Host species Manipulation factor Host system targeted Reference 78 helminth species: 64 Humans, animals, and plants Peptidases (61% of species) Immune system Helminth secretome data‑ nematodes, 7 trematodes, base (HSD) 7 cestodes (1) Garg and Ranganathan [15] Blood fuke Humans Proteins involved in calcium Neural system Knudsen et al. [12] Schistosoma mansoni (1) binding and regulation (afects cell signalization) Blood fuke Humans Paramyosin and SPO‑1 Immune system (evasion) Knudsen et al. [12] Schistosoma mansoni (1) Blood fuke Humans Proteases Immune system (degrada‑ Knudsen et al. [12] Schistosoma mansoni (1) tion of skin barriers) Liver fuke Molluscs (e.g. Galba trun- Proteases and antioxidant Immune system (evasion) Cwiklinski and Dalton [16] Fasciola hepatica (1) catula) enzymes: Gourbal et al. [13] Cu/Zn‑superoxide dis‑ mutase thioredoxin + Cestode Snakes Specifc proteins with no Unknown Kim et al. [17] Spirometra erinacei (1) Rhabdophis tigrinus identifed homologsa Cestode Rats Antigens Immune system Bień et al. [18] Hymenolepis diminuta (1) Rattus rattus (evasion and modulation) Baculovirus Silkworm Protein tyrosine Neural system (enhanced Kamita et al. [19] Bombyx mori NPV (2) Bombyx mori phosphatasea locomotory activity) Hairworm Grass‑hopper Meconema Wnta Neural system (modifca‑ Biron et al. [20] Spinochordodes tellinii Par- thalassinum cricket tions of monoamine [21] agordius tricuspidatus+ (2) Nemobius sylvestris+ levels) Protozoan Rat Tyrosine hydroxylasea Neural system (increases Prandovszky et al. [22] Toxoplasma gondii (2) Rattus rattus dopamine levels) Fungus Ant Camponotus pennsyl- Guanobutyric acid (GBA) and Neural system (action not De Bekker et al. [23] Ophiocordyceps unilateralis vanicus and sphingosine determined) (2) Formica dolosa Wasp Caterpillar Cytokinea Immune system (activation Adamo et al. [24] Cotesia congregata (2) Manduca sexta that results in feeding reduction) Wasp Cockroach Periplaneta Dopamine Neural system (represses the Libersat et al. [25] Ampulex compressa (2) americana activity of neurons) Aphid Witch hazel BICYCLE protein Development (induces Korgaonkar et al. [26] Hormaphis cornu (2) Hamamelis virginiana galls—novel plant ‘organs’) (1) Species of human importance. (2) Species studied in the context of behavioural manipulation. aProteins inferred from experimental or bioinformatics evidence, i.e. proteins not directly measured in the secretome Berger et al. Parasites Vectors (2021) 14:436 Page 3 of 20 consequences of the infection by S. solidus on the three- inside the S. solidus tegument, as shown through scan- spine stickleback’s morphology [30], physiology [31], ning and transmission electron microscopy [47]. Moreo- immune system [32], and behaviour [33] are well docu- ver, S. solidus excretes (through passive mechanisms) mented. For example, sticklebacks infected by S. solidus or secretes (through active mechanisms) molecules, show drastic behavioural changes that result in a loss of including (uncharacterized) proteins, and these secre- the anti-predator response [27]: infected fsh are more tions are sufcient to afect its fsh host behaviour [48]. exploratory [34], less anxious