In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein-protein interaction networks

Abstract

Background Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation and decreased production of meat, wool, and milk. Current diagnosis or treatment protocols are not fully effective and, thus, require further research of Cp pathogenesis.ResultsHere, we mapped known protein-protein interactions (PPI) from various species to nine Cp strains to reconstruct parts of the potential Cp interactome and to identify potentially essential proteins serving as putative drug targets. On average, we predict 16,669 interactions for each of the nine strains (with 15,495 interactions shared among all strains). An in silico sanity check suggests that the potential networks were not formed by spurious interactions but have a strong biological bias. With the inferred Cp networks we identify 181 essential proteins, among which 41 are non-host homologous.ConclusionsThe list of candidate interactions of the Cp strains lay the basis for developing novel hypotheses and designing according wet-lab studies. The non-host homologous essential proteins are attractive targets for therapeutic and diagnostic proposes. They allow for searching of small molecule inhibitors of binding interactions enabling modern drug discovery. Overall, the predicted Cp PPI networks form a valuable and versatile tool for researchers interested in Corynebacterium pseudotuberculosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0346-4) contains supplementary material, which is available to authorized users.

An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae

“…Some members of this family (nusG) has already been reported as drug target. Furthermore, rpsH and smpB are also reported as potential drug target by Folador et al, 2016 in their in silico study [ 41 ]. Protein DIP1084 is Putative iron transport membrane protein (FecCD-family) and DIP0983 is uncharacterized Hypothetical Protein that need to be characterized experimentally.…”

Functional Analysis of Hypothetical Proteins of Vibrio parahaemolyticus Reveals the Presence of Virulence Factors and Growth-Related Enzymes With Therapeutic Potential

“…The interolog mapping approach was used to translate the identified interactions to V. parahaemolyticus MSR16 and MSR17 strains, which implies that when two proteins interact, their orthologous partners would also interact. 59 - 61 STRING, as described in eggNOG, exploits hierarchically organized orthologous group relations to retrieve association between relevant species. 62 - 64 …”

Computational Network Inference for Bacterial Interactomics

“…Using interolog mapping, 12 putative drug targets were identified in methicillin-resistant Staphylococcus aureus , including a histone deacetylase ( 241 ). A predicted Corynebacterium pseudotuberculosis interactome was used to identify 41 essential proteins as candidates for infection diagnosis in livestock, highlighting the tryptophan biosynthesis pathway as a potential drug target ( 200 ). The network also revealed that this species may use multiple iron acquisition strategies in low iron environments.…”