Dataset Information

N-terminomics profiling of host proteins targeted by excretory-secretory proteases of the nematode Angiostrongylus vasorum identifies points of interaction with canine coagulation and complement cascade

ABSTRACT: The cardiopulmonary nematode Angiostrongylus vasorum can cause severe disease in dogs, including coagulopathies manifesting with bleeding. We analysed A. vasorum excretory/secretory protein (ESP)-treated dog plasma and serum by N-terminome analysis using Terminal Amine Isotopic Labelling of Substrates (TAILS) to identify cleaved host substrates. In plasma and serum samples 430 and 475 dog proteins were identified, respectively. A total of eight dog proteins were significantly increasingly cleaved upon exposure to A. vasorum ESP: of these, three were coagulation factors (factor II, V and IX) and three were complement proteins (complement C3, C4-A and C5). Comparison with human motif sequence orthologues revealed known cleavage sites in coagulation factor IX and prothrombin. These and further identified cleavage sites suggest direct or indirect activation or proteolysis of complement and coagulation components through A. vasorum ESP, which contains several proteases. Further studies are needed to validate their substrate specificity.

INSTRUMENT(S):

ORGANISM(S): Canis Familiaris (dog) (canis Lupus Familiaris) Angiostrongylus Vasorum

TISSUE(S): Blood Plasma, Blood Serum

SUBMITTER: Nina Germitsch

LAB HEAD: Manuela Schnyder

PROVIDER: PXD056659 | Pride | 2025-05-07

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20200626_006_S219315_TAILS_P_10plex_post_rep.raw	Raw
	20200626_007_S219314_TAILS_P_10plex_pre.raw	Raw
	20200626_008_S219313_TAILS_S_10plex_post.raw	Raw
	20200626_009_S219312_TAILS_S_10plex_pre.raw	Raw
	20200626_011_S219315_TAILS_P_10plex_post.raw	Raw

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Publications

N-terminomics profiling of host proteins targeted by excretory-secretory proteases of the nematode Angiostrongylus vasorum identifies points of interaction with canine coagulation and complement cascade.

Germitsch Nina N Kockmann Tobias T Schnyder Manuela M Tritten Lucienne L

PloS one 20250115 1

The cardiopulmonary nematode Angiostrongylus vasorum can cause severe disease in dogs, including coagulopathies manifesting with bleeding. We analysed A. vasorum excretory/secretory protein (ESP)-treated dog plasma and serum by N-terminome analysis using Terminal Amine Isotopic Labelling of Substrates (TAILS) to identify cleaved host substrates. In plasma and serum samples 430 and 475 dog proteins were identified, respectively. A total of eight dog proteins were significantly cleaved at higher l ...[more]

PMID: 39813225

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Project description:The equine bloodworm, Strongylus vulgaris, is a highly pathogenic parasite causing potentially fatal vascular and intestinal damage. Parasites express and release microRNAs (miRNAs) for internal regulation and to modulate host immunity. The microRNAome (miRNAome) of S. vulgaris remains unannotated and the aim of this study was to annotate the miRNAome of 4th (L4) and 5th (L5) stage larvae of S. vulgaris and to examine differences in miRNA abundance between larval stages and sexes. Furthermore, we aimed to determine if miRNAs were detectable in excretory/secretory products (ESP) from larvae and in arterial tissue from their predilection site, the Cranial Mesenteric Artery (CMA). Larvae were collected from naturally infected foals, and categorized by sex and stage. A subset of larvae was snap-frozen, while the remaining were incubated and the excretory/secretory products (ESP) collected. Arterial tissue samples were collected from the CMA. Small RNA sequencing followed by a custom bioinformatic pipeline was used for annotation. We identified 142 S. vulgaris miRNAs in larvae and 136 in ESP. Significant differences in miRNA abundance were observed between larvae and ESP, and between L5 females (L5Fs) and L5 males (L5Ms), L4s and L5Fs and L4s and L5Ms. No differences were found between L4s and L5s overall. In ESP, several miRNAs were differentially abundant across all groups. Validation through quantitative real-time PCR (qPCR) detected selected miRNAs and their differential abundance in larvae and ESP. One parasite-derived miRNA was detected in some of the horse arterial tissue samples but at very low levels. This study provided the first annotation of the S. vulgaris miRNAome. Most of the annotated larvae miRNAs were also detectable in ESP and differences in miRNA abundance between sexes were found for larvae, and between sexes and stages for ESP. Parasite-derived miRNAs were, however, not consistently detectable in the surrounding host arterial tissue.