Genetic makeup ofTrichuris hominibus, a novelTrichurisspecies naturally infecting humans and displaying signs of resistance to drug treatment

Abstract

Abstract Trichuriasis is a neglected tropical disease that affects as many as 500 million individuals and can cause significant morbidity, even death. 1 For decades, it is thought to be caused by one species of Whipworm, Trichuris trichiura . Discrepancies in response rates to benzimidazole treatment for trichuriasis exist across clinical trial reports, and the emergence of anthelmintic resistance is predicted to be established within the next decade. 2,3 However, data that addresses these discrepancies and provides evidence for resistance does not exist. Here, we present the discovery of a novel Trichuris species, Trichuris hominis , causing Trichuriasis, and we provide genomic evidence that supports the establishment of drug resistance in humans. Combining long- and short-read sequencing approaches, we assembled a high-quality reference genome of Trichuris hominis to construct the species tree of the Trichuris genus and we sequenced a total of 752 individual worms which confirmed the phylogenetic placement and provided evidence supporting benzimidazole resistance. Gene duplication events across the species tree and a genome wide association study point towards β-tubulin variations as a source of albendazole resistance. Our results demonstrate how trichuriasis can be caused by more than one species of whipworm and that this species carries genomic variations conferring with drug resistance in humans. We anticipate our findings to have a profound impact on how we understand whipworm infections with implications on all present and future de-worming strategies across the globe. Efforts should support the development of species-level diagnostic tools, patient-centric treatment approaches in addition to mass-drug administration strategies, the definition of species-specific standard-of-care guidelines, and the incorporation of species diversity in vaccine development.