Myxozoan Adhesion and Virulence: Ceratonova shasta on the Move

Abstract

Motility factors are fundamental for parasite invasion, migration, proliferation and immune evasion and thus can influence parasitic disease pathogenesis and virulence. Salmonid enteronecrosis is caused by a myxozoan (Phylum Cnidarian) parasite, Ceratonova shasta. Three parasite genotypes (0, I, II) occur, with varying degrees of virulence in its host, making it a good model for examining the role of motility in virulence. We compare C. shasta cell motility between genotypes and describe how the cellular protrusions interact with the host. We support these observations with motility gene expression analyses. C. shasta stages can move by single or combined used of filopodia, lamellipodia and blebs, with different behaviors such as static adhesion, crawling or blebbing, some previously unobserved in myxozoans. C. shasta stages showed high flexibility of switching between different morphotypes, suggesting a high capacity to adapt to their microenvironment. Exposure to fibronectin showed that C. shasta stages have extraordinary adhesive affinities to glycoprotein components of the extracellular matrix (ECM). When comparing C. shasta genotypes 0 (low virulence, no mortality) and IIR (high virulence, high mortality) infections in rainbow trout, major differences were observed with regard to their migration to the target organ, gene expression patterns and proliferation rate in the host. IIR is characterized by rapid multiplication and fast amoeboid bleb-based migration to the gut, where adhesion (mediated by integrin-β and talin), ECM disruption and virulent systemic dispersion of the parasite causes massive pathology. Genotype 0 is characterized by low proliferation rates, slow directional and early adhesive migration and localized, non-destructive development in the gut. We conclude that parasite adhesion drives virulence in C. shasta and that effectors, such as integrins, reveal themselves as attractive therapeutic targets in a group of parasites for which no effective treatments are known.

A tale of two fish: Comparative transcriptomics of resistant and susceptible steelhead following exposure to Ceratonova shasta highlights differences in parasite recognition

“…shasta reaches the intestine via blood vessels and then migrates through the tissue layers to release spores into the intestinal lumen. As recently shown by Alama-Bermejo et al [ 109 ], C . shasta genotype II is highly mobile and has strong adhesive affinities for the glycoprotein components of the extracellular matrix (ECM), resulting in massive interaction and disruption of the host intestinal ECM.…”

Transcriptome-Wide Comparisons and Virulence Gene Polymorphisms of Host-Associated Genotypes of the Cnidarian Parasite Ceratonova shasta in Salmonids

“…For example, the capacity of Toxoplasma gondii for migration, both across tissues and over long distances, characterizes its virulence ( Barragan and Sibley 2002 ). Developmental stages of C. shasta are motile and capable of producing different cell protrusions (filopodia, lamellipodia, and blebs), with specific functions such as anchoring/adhesion, crawling, and blebbing ( Alama-Bermejo et al. 2019 ).…”

“…2012 : Stinson and Bartholomew 2012 ). In vivo observations reveal that IIR infection is characterized by rapid proliferation, fast amoeboid bleb-based motility, and high adhesion, with significant differential expression (by quantitative PCR) of key motility and adhesive factors between type 0 (low virulent) and IIR (highly virulent) genotypes in rainbow trout ( Alama-Bermejo et al. 2019 ).…”

Genetic Diversity of Serine Protease Inhibitors in Myxozoan (Cnidaria, Myxozoa) Fish Parasites

“…The biodiversity of these parasites is remarkable and a result of host-associated cospeciation [ 2 , 3 , 4 ]. Developmental stages of myxozoans are motile during invasion, migration, and proliferation due to cellular processes that enable unique cell motility [ 5 , 6 , 7 , 8 ]. Myxozoans affect the health of both farmed and wild fish populations, causing diseases and mortality.…”