Sustainable gastrointestinal parasite control in small ruminants

Abstract

Gastrointestinal nematode infections cause severe production losses in sheep, but intensive anthelmintic use has led to widespread resistance. Therefore, alternative control strategies are needed. This dissertation implements a multi-pronged approach combining broad in vitro screening, phytochemical profiling, and host transcriptomics to identify sustainable parasite-control solutions. The first experiment focused on evaluating aqueous extracts of 24 plant species (forages, common weeds and herbs) in larval mortality assays against infective H. contortus and S. papillosus. Several extracts caused >70 percent mortality by 48 h. The most effective extracts were from species such as Ageratum conyzoides and Chenopodium album. To investigate the cause of antiparasitic effect of those plant extracts, the second experiment further investigated untargeted LC-MS/MS metabolomics of the active extracts and in silico docking to three H. contortus target proteins. From 1,370 detected metabolites, 72 compounds enriched in the most effective extracts were prioritized. Key candidates included flavonoids, terpenoids, alkaloids, phenolic compounds and other bioactive compounds. Although botanical interventions may offer an alternative to chemical dewormers, sustainable parasite control also depends on improving the host's innate ability to resist infection. Therefore, the last chapter examined phenotypic and transcriptomic signatures of GIN resistance in Katahdin sheep. Ten ewes were selected based on fecal egg count (FEC) at three times. RNA from both whole blood and fecal samples was sequenced and analyzed. Blood RNA-seq identified 19 differentially expressed genes at the first time point and 13 DEGs at the second time point, including candidate immune genes (e.g., C3AR1, ADGRE3, ATP5IF1, ALAS2) and three consistently upregulated long non-coding RNAs (lcRNA) in resistant ewes. In contrast, fecal-derived host RNA showed low mapping rates to the ovine genome and yielded no significant differential expression. Though no DEGs were displayed in fecal samples between the two groups, approximately 8,600 ovine genes were annotated, therefore, further study in a larger sample size may validate the feasibility of this non-invasive approach in sheep. Collectively, these studies identified potential and critical roles of the plant extracts and gene candidates, respectively, that may be useful for implementing organic gastrointestinal nematode control in small ruminants.