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Toward novel treatment against filariasis: Insight into genome-wide co-evolutionary analysis of filarial nematodes and Wolbachia
- Source :
- Frontiers in Microbiology. 14
- Publication Year :
- 2023
- Publisher :
- Frontiers Media SA, 2023.
-
Abstract
- Peer reviewed: True<br />Acknowledgements: We thank Prapon Wilairat and Thanat Chookajorn for their comments on the scope of work during its initial stage. We thank David Ochou for additional insight into the use of the mirrortree approach and helpful discussion. We thank James Cotton for providing the assembly of Wolbachia of B. pahangi used in this analysis. We thank members of the Parasite Genomics team at the Wellcome Sanger Institute for their comments, discussions, and insights; in particular, we thank Matt Berriman, James Cotton, Eleanor Stanley, Martin Hunt, Hayley Bennett, and Anna Protasio. Computationally demanding data analyses were performed on high-performance computing facilities at Wellcome Sanger Institute and Khon Kaen University’s Office of Digital Technology.<br />Infectious diseases caused by filarial nematodes are major health problems for humans and animals globally. Current treatment using anti-helminthic drugs requires a long treatment period and is only effective against the microfilarial stage. Most species of filarial nematodes harbor a specific strain of Wolbachia bacteria, which are essential for the survival, development, and reproduction of the nematodes. This parasite-bacteria obligate symbiosis offers a new angle for the cure of filariasis. In this study, we utilized publicly available genome data and putative protein sequences from seven filarial nematode species and their symbiotic Wolbachia to screen for protein-protein interactions that could be a novel target against multiple filarial nematode species. Genome-wide in silico screening was performed to predict molecular interactions based on co-evolutionary signals. We identified over 8,000 pairs of gene families that show evidence of co-evolution based on high correlation score and low false discovery rate (FDR) between gene families and obtained a candidate list that may be keys in filarial nematode-Wolbachia interactions. Functional analysis was conducted on these top-scoring pairs, revealing biological processes related to various signaling processes, adult lifespan, developmental control, lipid and nucleotide metabolism, and RNA modification. Furthermore, network analysis of the top-scoring genes with multiple co-evolving pairs suggests candidate genes in both Wolbachia and the nematode that may play crucial roles at the center of multi-gene networks. A number of the top-scoring genes matched well to known drug targets, suggesting a promising drug-repurposing strategy that could be applicable against multiple filarial nematode species.
Details
- ISSN :
- 1664302X
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Frontiers in Microbiology
- Accession number :
- edsair.doi.dedup.....c02d1735d60d6718d4d36a03d68fabdc
- Full Text :
- https://doi.org/10.3389/fmicb.2023.1052352