Multi-stage transcriptome profiling of the neglected food-borne echinostome Artyfechinostomum sufrartyfex reveal potential diagnostic and drug targets

Abstract

Lack of effective surveillance and control methods for neglected helminth diseases particularly in context of rural areas in India is a serious concern in terms of public health. With regard to the emerging food-borne echinostomid Artyfechinostomum sufrartyfex infection in the country, the current study is an in silico attempt to screen for plausible diagnostic and drug targets against the trematode. Transcriptome of adult, encysted and excysted metacercaria stages of the parasite was generated using Illumina sequencing platform. A de-novo assembly strategy utilizing transcriptome data generated from the three lifecycle stages was followed to generate the representative transcripts. Longest open reading frames identified for the transcripts were further conceptually translated into their respective protein sequences. Detailed analysis of this dataset through various bioinformatics pipelines and tools eventually identified 14 credible diagnostic and 10 drug targets along with their FDA-approved and ZINC molecules. Some of the important diagnostic candidates include thioredoxin peroxidase, haemoglobinase, cathepsin L, cathepsin L-like and B-like cysteine proteases. Among the drug targets, uncharacterized sodium dependent transporter and bifunctional protein Aas were identified as top targets exhibiting significant interaction with Rifamycin and ZINC02820058 molecule, respectively. Further, B-cell epitope analysis of the diagnostic targets revealed unique epitopes for 10 of them thus indicating their potential role in specific diagnosis of the parasite. The diagnostic candidates along with a number of lesser known drug targets and their ligand molecules identified in this study provides a reasonable basis for evaluation and development of future intervention strategies against A. sufrartyfex.