Network-Based Analysis of Virulence Factors for Uncovering Aeromonas Veronii Pathogenesis

Abstract

Background: Aeromonas veronii is a pathogen that causes serious harm to aquaculture. Virulence factors are its pathogenic basis, which could promote pathogens to colonize the host, evade host defense and so on. But because experimental verification of virulence factors is time-consuming and laborious, the number of known virulence factors is limited. In this past, most studies only focused on single virulence factor, resulting the biased interpretation for pathogenesis.Results: In this study, a protein-protein interaction (PPI) network at genome-wide scale for A. veronii was first constructed. Then, virulence factors were predicted and mapped on the network. Topological characteristics of the virulence factors were analyzed. The results showed that the virulence factors had higher degree and betweenness centrality than the other proteins in the network. In particular, the virulence factors tended to interact with each other and were enriched in two network modules. One of the modules mainly consisted of histidine kinases, response regulators, diguanylate cyclases and phosphodiesterases, which played important roles in two-component regulatory systems and the synthesis and degradation of cyclic-diGMP. Furthermore, an interspecies PPI network between A. veronii and its host Oreochromis niloticus was also constructed. The structures and interacting sites of the virulence factors and host proteins were added to the interspecies PPI network. By analyzing the interspecies PPI network, we found that the virulence factors could competitively bind host proteins and some of the interacting sites of the virulence factors were shared by different host proteins. Drugs could be designed to target these sites and further prevent pathogen to interfere with host pathways.Conclusions: Our results indicated that the virulence factors regulated the virulence of A. veronii by involving in signal transduction pathway and manipulate host biological processes by mimicking and competitively binding host proteins. Our results deepened the understanding for pathogenesis and had important theoretical significance for designing targeted antibacterial drugs.