Protein–protein interaction network and potential drug target candidates ofStreptococcus suis

Abstract

Aims: This study aimed to explore potential drug targets of Streptococcus suis at the system level. Methods and Results: A homologous protein mapping method was used in the construction of a protein-protein interaction (PPI) network of S. suis, which presented 1147 non-redundant interaction pairs among 286 proteins. The parameters of PPI networks were calculated and showed scale-free network properties. In all, 41 possibly essential proteins identified from 47 highly connected proteins were selected as potential drug target candidates. Of these proteins, 30 were already regarded as drug targets in other bacterial species. Six transporters with high connections to other functional proteins were identified as probably not essential but important functional proteins. Afterward, the subnetwork centred with cell division protein FtsZ was used in confirming the PPI network through bacterial two-hybrid analysis. Conclusions: The predicted PPI network covers 13Á04% of the proteome in S. suis. The selected 41 potential drug target candidates are conserved between S. suis and several model bacteria. Significance and Impact of the Study: The predictions included proteins known to be drug targets, and a verifying experiment confirmed the reliability of predicted interactions. This work is the first to present systematic computational PPI data for S. suis and provides potential drug targets, which are valuable in exploring novel anti-streptococcus drugs.Studies on PPIs reveal the underlying molecular mechanism in living cells, predict protein functions, separate functional modules, identify essential genes and pathways, and search novel drug targets (Peng et al. 2017). With the increasing availability of genomics, proteomics, metabolomics and bioinformatics, the amount of proteome level PPI data from experiments based on various highthroughput experimental methods is growing rapidly in many model organisms (Lees et al. 2011).Exploring the PPI networks of pathogens at the system level can be a useful and effective strategy for investigating potential drug targets, such as species-specific genes, uncharacterized essential genes, virulence genes and membrane transporters (Hasan et al. 2016). A series of