Advances in the Molecular and Cellular Biology of Strongyloides spp.

Abstract

Abstract Purpose of Review This paper constitutes an update of recent studies on the general biology, molecular genetics, and cellular biology of Strongyloides spp. and related parasitic nematodes. Recent Findings Increasingly, human strongyloidiasis is considered the most neglected of neglected tropical diseases. Despite this, the last 5 years has seen remarkable advances in the molecular biology of Strongyloides spp. Genome sequences for S. stercoralis, S. ratti, S. venezuelensis, S. papillosus, and the related parasite Parastrongyloides trichosuri were created, annotated, and analyzed. These genomic resources, along with a practical transgenesis platform for Strongyloides spp., aided a major achievement, the advent of targeted mutagenesis via CRISPR/Cas9 in S. stercoralis and S. ratti. The genome sequences have also enabled significant molecular epidemiologic and phylogenetic findings on human strongyloidiasis, including the first genetic evidence of zoonotic transmission of S. stercoralis between dogs and humans. Studies of molecular signaling pathways identified the nuclear receptor Ss-DAF-12 as one that can be manipulated in the parasite by exogenous application of its steroid ligands. The chemotherapeutic implications of this were unscored by a study in which a Ss-DAF-12 ligand suppressed autoinfection by S. stercoralis in a new murine model of human strongyloidiasis. Summary Seminal advances in genomics of Strongyloides spp. have transformed research into strongyloidiasis, facilitating fundamental phylogenetic and epidemiologic studies and aiding the deployment of CRISPR/Cas9 gene disruption and editing as functional genomic tools in Strongyloides spp. Studies of Ss-DAF-12 signaling in S. stercoralis demonstrated the potential of this pathway as a novel chemotherapeutic target in parasitic nematodes.