Protein-protein interaction network and potential drug target candidates of Streptococcus suis

J Appl Microbiol. 2021 Aug;131(2):658-670. doi: 10.1111/jam.14950. Epub 2021 Mar 9.

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 13·04% 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.

Keywords: Streptococcus suis; FtsZ; bacterial two-hybrid; drug target; homologous protein mapping; protein-protein interaction network.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism*
  • Membrane Transport Proteins / metabolism
  • Protein Interaction Mapping*
  • Proteome / metabolism
  • Streptococcus suis / drug effects
  • Streptococcus suis / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Transport Proteins
  • Proteome