Network Biology, 2023, 13(4): 137-154
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Host-Pathogen protein-protein interactions reveal the key mechanisms behind the endosymbiotic association of Wolbachia with Brugia malayi

Amresh Kumar Sharma, Aparna Chaturvedi, Anup Som
Centre of Bioinformatics, Institute of Interdisciplinary Studies, University of Allahabad, Prayagraj-211002, India

Received 27 April 2023;Accepted 15 May 2023;Published online 25 May 2023;Published 1 December 2023

Wolbachia are gram-negative endosymbiotic bacteria residing in the nematode host Brugia malayi that causes lymphatic filariasis in humans. Wolbachia settle in the host environment for their survival, growth and reproduction by maintaining an obligate mutualism relationship. However, the mechanism used by Wolbachia to maintain its mutualistic relationship with the nematode is poorly understood. Therefore, to elucidate the host-pathogen interaction (HPI) mechanism of Wolbachia and Brugia malayi, we used interolog-based approach for identification of host-pathogen protein-protein interactions (HP-PPIs) network and domain-based approach for the validation. The inter-species HP-PPIs network contained 392 proteins (258 Brugia malayi and 134 Wolbachia proteins) connected by 829 edges. Further, based on interolog approach, we identified 24 pathogen (Wolbachia) and 33 host (Brugia malayi) proteins involved in HPI. This study also reported 8 hub genes namely bma-atp-1, Bm1_25145, A0A0K0JKQ9, fusA, bma-eef-2, rplB, Bma-rpl-2, and bma-eftu-2 involved in maintaining an endosymbiotic relationship between Wolbachia and Brugia malayi. Furthermore, we also reported six-pair of host-pathogen interactions containing numerous pairs of shared domains that might be crucial for the establishment of mutualistic relationship between Wolbachia and Brugia malayi. The functional analysis revealed most of the Brugia malayi proteins are involved in the generation of precursor metabolites showing catalytic activity in the intracellular anatomical structures and organelles. The subcellular localization reported host and pathogen proteins were located in mitochondria and cytoplasm respectively. The Brugia malayi pathways involved in HPI were metabolic pathway, oxidative phosphorylation pathway, and spliceosome pathways, indicates that for maintaining mutualism energy-yielding pathways are targeted. Overall, this work provides new insights into the mechanism of HPIs between Wolbachia and Brugia malayi, and will help researchers a deeper understanding of the intracellular pathogenic activity and endosymbiotic relationship of Wolbachia with its host Brugia malayi.

Keywords Wolbachia;Brugia malayi;host-pathogen interaction;Interologs;domain-domain interaction;enrichment analysis;Metabolic pathway;network biology.

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