Comparative transcriptome profiles of first-stage larvae and adult female Dracunculus medinensis (Guinea worm)

Abstract

Dracunculus medinensis, also called the Guinea worm, is a nematode that causes dracunculiasis, a debilitating neglected tropical disease in humans. The parasite is currently targeted by the global Guinea Worm Eradication Program (GWEP). Historically, GWEP in endemic countries have focused on interrupting transmission of the disease through intervention such as isolation and management of patients, health education, provision of improved water sources and promotion of filtering drinking water to avoid ingestion of the copepod intermediate host (IH) that may contain infectious third-stage larvae. The recent shift of Guinea worm infections in animals - particularly domestic dogs - has introduced an additional challenge to the eradication program, underscoring the urgent need for diagnostics and therapeutics. Understanding the parasite biology and survival strategies in the mammalian host, the copepod IH, and fresh water is pivotal to identifying new control measures. Comparative transcriptomic analysis provides a powerful tool to uncover the molecular mechanisms underlying parasite survival and adaptations. Here, we compared the transcriptome of adult gravid female and first-stage larvae (L1), the stage infective for the copepod IH. Comparative transcriptomic analysis of two adult females and their L1 revealed an upregulation of genes involved in translation, transcription, and DNA repair in L1, likely reflecting adaptations essential for survival in freshwater and subsequent infection of copepods. Additionally, genes involved in cuticle formation were upregulated in adult females highlighting the role of cuticle integrity in retaining millions of L1 until the gravid female worm emerges. We identified highly expressed genes in the adult female that may represent promising candidates for diagnostic markers. This study provides novel insights into the biology of the Guinea worm by examining the transcriptome of L1 and adult female stages. These findings could support the development of novel diagnostics and therapeutics to advance the ongoing eradication effort. Authors summaryGuinea worm disease is caused by the nematode Dracunculus medinensis, a parasitic worm responsible for a debilitating neglected tropical disease in humans and targeted for global eradication. Infection occurs through the consumption of contaminated drinking water with the infective larval stage harbored within fresh water crustacean copepods - the intermediate host of the parasite. The high number of Guinea worm infections in animals specially dogs poses a significant challenge to eradication, as infected animals act as reservoirs, contributing to the parasites persistence in the environment. Furthermore, the absence of early diagnostic tools and effective therapeutics complicates disease control. In this study, we performed a comparative transcriptome analysis of adult female Guinea worms and their first-stage larvae. We identified highly expressed genes in the adult female that may represent promising candidates for diagnostic markers. Additionally, we found genes and pathways upregulated in first-stage larvae which are likely essential for survival in freshwater and subsequent infection of copepods. Our study provides insight into the molecular mechanisms underlying Guinea worm survival across life stages and environments. These findings aim to support the development of novel diagnostics and therapeutics to advance ongoing eradication efforts of this neglected tropical disease.