Toward novel treatment against filariasis: Insight into genome-wide co-evolutionary analysis of filarial nematodes and Wolbachia

Frontiers in Microbiology

Microbiology

Jutarop Phetcharaburanin¹  Watcharin Loilome¹  Poramate Klanrit¹  Nisana Namwat¹  Siriyakorn Kulwong¹  Arporn Wangwiwatsin¹  Wanchai Maleewong²  Adam J. Reid³ 

[1] Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand;Khon Kaen University Phenome Centre, Khon Kaen University, Khon Kaen, Thailand;Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;Parasite Genomics Group, Wellcome Sanger Institute, Hinxton, United Kingdom;The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom;

关键词: filarial nematode;    Wolbachia;    co-evolution;    mirrortree;    protein–protein interactions;    genomics;   

DOI  :  10.3389/fmicb.2023.1052352

 received in 2022-09-26, accepted in 2023-02-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Wangwiwatsin, Kulwong, Phetcharaburanin, Namwat, Klanrit, Loilome, Maleewong and Reid.