Dataset Information

Toxicity and Immunogenicity of a Tardigrade Cytosolic Abundant Heat Soluble Protein in Mice.

ABSTRACT: Tardigrades are microscopic animals well-known for their stress tolerance, including the ability to survive desiccation. This survival requires cytosolic abundant heat soluble (CAHS) proteins. CAHS D protects enzymes from desiccation- and lyophilization-induced inactivation in vitro and has the potential to stabilize protein-based therapeutics, including vaccines. Here, we investigate whether purified recombinant CAHS D causes hemolysis or a toxic or immunogenic response following intraperitoneal injection in mice. CAHS D did not cause hemolysis, and all mice survived the 28-day monitoring period. The mice gained weight normally and developed anti-CAHS D antibodies but did not show upregulation of the inflammatory cytokines interleukin-6 and tumor necrosis factor alpha. In summary, CAHS D is not toxic and does not promote an inflammatory immune response in mice under the conditions used here, suggesting the reasonability of further study for use as stabilizers of protein-based therapeutics.

SUBMITTER: Esterly HJ

PROVIDER: S-EPMC7577191 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Toxicity and Immunogenicity of a Tardigrade Cytosolic Abundant Heat Soluble Protein in Mice.

Esterly Harrison J HJ Crilly Candice J CJ Piszkiewicz Samantha S Shovlin Dane J DJ Pielak Gary J GJ Christian Brooke E BE

Frontiers in pharmacology 20201007

Tardigrades are microscopic animals well-known for their stress tolerance, including the ability to survive desiccation. This survival requires cytosolic abundant heat soluble (CAHS) proteins. CAHS D protects enzymes from desiccation- and lyophilization-induced inactivation <i>in vitro</i> and has the potential to stabilize protein-based therapeutics, including vaccines. Here, we investigate whether purified recombinant CAHS D causes hemolysis or a toxic or immunogenic response following intrape ...[more]

PMID: 33117164

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Project description:BackgroundMany limno-terrestrial tardigrades can enter an ametabolic state, known as anhydrobiosis, upon desiccation, in which the animals can withstand extreme environments. Through genomics studies, molecular components of anhydrobiosis are beginning to be elucidated, such as the expansion of oxidative stress response genes, loss of stress signaling pathways, and gain of tardigrade-specific heat-soluble protein families designated CAHS and SAHS. However, to date, studies have predominantly investigated the class Eutardigrada, and molecular mechanisms in the remaining class, Heterotardigrada, still remains elusive. To address this gap in the research, we report a multiomics study of the heterotardigrade Echiniscus testudo, one of the most desiccation-tolerant species which is not yet culturable in laboratory conditions.ResultsIn order to elucidate the molecular basis of anhydrobiosis in E. testudo, we employed a multi-omics strategy encompassing genome sequencing, differential transcriptomics, and proteomics. Using ultra-low input library sequencing protocol from a single specimen, we sequenced and assembled the 153.7 Mbp genome annotated using RNA-Seq data. None of the previously identified tardigrade-specific abundant heat-soluble genes was conserved, while the loss and expansion of existing pathways were partly shared. Furthermore, we identified two families novel abundant heat-soluble proteins, which we named E. testudo Abundant Heat Soluble (EtAHS), that are predicted to contain large stretches of disordered regions. Likewise the AHS families in eutardigrada, EtAHS shows structural changes from random coil to alphahelix as the water content was decreased in vitro. These characteristics of EtAHS proteins are analogous to those of CAHS in eutardigrades, while there is no conservation at the sequence level.ConclusionsOur results suggest that Heterotardigrada have partly shared but distinct anhydrobiosis machinery compared with Eutardigrada, possibly due to convergent evolution within Tardigrada. (276/350).

Dataset Information

Toxicity and Immunogenicity of a Tardigrade Cytosolic Abundant Heat Soluble Protein in Mice.

Publications

Toxicity and Immunogenicity of a Tardigrade Cytosolic Abundant Heat Soluble Protein in Mice.

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