The Molecular Mechanisms Employed by the Parasite Myxobolus bejeranoi (Cnidaria: Myxozoa) from Invasion through Sporulation for Successful Proliferation in Its Fish Host

Abstract

Myxozoa is a unique group of obligate endoparasites in the phylum Cnidaria that can cause emerging diseases in wild and cultured fish populations. Recently, we identified a new myxozoan species, Myxobolus bejeranoi, which infects the gills of cultured tilapia while suppressing host immunity. To uncover the molecular mechanisms underlying this successful parasitic strategy, we conducted transcriptomics analysis of M. bejeranoi throughout the infection. Our results show that histones, which are essential for accelerated cell division, are highly expressed even one day after invasion. As the infection progressed, conserved parasitic genes that are known to modulate the host immune reaction in different parasitic taxa were upregulated. These genes included energy-related glycolytic enzymes, as well as calreticulin, proteases, and miRNA biogenesis proteins. Interestingly, myxozoan calreticulin formed a distinct phylogenetic clade apart from other cnidarians, suggesting a possible function in parasite pathogenesis. Sporogenesis was in its final stages 20 days post-exposure, as spore-specific markers were highly expressed. Lastly, we provide the first catalog of transcription factors in a Myxozoa species, which is minimized compared to free-living cnidarians and is dominated by homeodomain types. Overall, these molecular insights into myxozoan infection support the concept that parasitic strategies are a result of convergent evolution.

The myxozoans Myxobolus cerebralis and Tetracapsuloides bryosalmonae modulate rainbow trout immune responses: quantitative shotgun proteomics at the portals of entry after single and co-infections

“…The M. cerebralis histone was found connected to host proteins in the protein–protein interaction network. This protein is likely essential for accelerated cell division and myxozoan stage differentiation, as seen in a previous study of Myxobolus bejeranoi where differential expression of histones were found to be associated with parasitic invasion ( Maor-Landaw et al., 2023 ). Calmodulin was also involved in the gill protein-protein interaction network, and is likely a key virulence factor that contributes to parasite motility and invasion of myxozoan parasites, as reported for other parasites ( Long et al., 2017 ).…”

The Tilapia Cyst Tissue Enclosing the Proliferating Myxobolus bejeranoi Parasite Exhibits Cornified Structure and Immune Barrier Function

“…Free hemoglobin, the product of hemolysis, can be induced by various pathogens [ 49 ], which was recently reported as a feeding behavior of the myxozoan Sphaerospora molnari [ 50 , 51 ]. Upon infection, M. bejeranoi deploys an array of activated proteases, including cathepsin D and cathepsin L [ 29 ], which may act to degrade hemoglobin, as in other parasites [ 32 , 52 ]. This aligns with our findings, indicating decrease in globin proteins and an increase in endocytosis, the process in which macrophages engulf their targets [ 47 ].…”

“…Myxozoan parasites exploit their host and migrate through its tissues using a battery of secreted proteolytic enzymes [ 29 , 32 , 52 , 53 , 54 , 55 ]. Thus, a vital component in the host immune arsenal is protease inhibitors [ 56 ].…”

“…As sporogenesis progresses, M. bejeranoi cells continue to proliferate inside the cysts and the number of oxygen-consuming cells increases, leading to hypoxic conditions [ 29 ]. Nevertheless, we did not observe signs of angiogenesis in the host connective tissue, such as in the case of Myxobolus pendula , where the host vascular network was suggested to provide the parasite with nutrients and oxygen [ 42 ].…”

“…M. bejeranoi is a highly efficient parasite that is capable of rapid proliferation within its host. Upon infection, M. bejeranoi cells express genes, such as histones, that facilitate rapid cell divisions and proper supply of the required energy [ 29 , 30 ]. Further, similar to other parasites [ 29 , 31 , 32 ], it employs tactics, such as an increase in calreticulin and an arsenal of proteases, to invade host tissues and eventually shut down its immune system [ 6 ].…”