Conserved host-pathogen PPIs: Globally conserved inter-species bacterial PPIs based conserved host-pathogen interactome derived novel target in C. pseudotuberculosis, C. diphtheriae, M. tuberculosis, C. ulcerans, Y. pestis, and E. coli targeted by Piper betel compounds

Debmalya Barh, Krishnakant Gupta, Neha Jain, Gourav Khatri, Nidia León-Sicairos, Adrian Canizalez-Roman, Sandeep Tiwari, Ankit Verma, Sachin Rahangdale, Syed Shah Hassan, Anderson Rodrigues Dos Santos, Amjad Ali, Luis Carlos Guimarães, Rommel Thiago Jucá Ramos, Pratap Devarapalli, Neha Barve, Marriam Bakhtiar, Ranjith Kumavath, Preetam Ghosh, Anderson MiyoshiArtur Silva, Anil Kumar, Amarendra Narayan Misra, Kenneth Blum, Jan Baumbach, Vasco Azevedo

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Although attempts have been made to unveil protein-protein and host-pathogen interactions based on molecular insights of important biological events and pathogenesis in various organisms, these efforts have not yet been reported in Corynebacterium pseudotuberculosis (Cp), the causative agent of Caseous Lymphadenitis (CLA). In this study, we used computational approaches to develop common conserved intra-species protein-protein interaction (PPI) networks first time for four Cp strains (Cp FRC41, Cp 316, Cp 3/99-5, and Cp P54B96) followed by development of a common conserved inter-species bacterial PPI using conserved proteins in multiple pathogens (Y. pestis, M. tuberculosis, C. diphtheriae, C. ulcerans, E. coli, and all four Cp strains) and E. Coli based experimentally validated PPI data. Furthermore, the interacting proteins in the common conserved inter-species bacterial PPI were used to generate a conserved host-pathogen interaction (HP-PPI) network considering human, goat, sheep, bovine, and horse as hosts. The HP-PPI network was validated, and acetate kinase (Ack) was identified as a novel broad spectrum target. Ceftiofur, penicillin, and two natural compounds derived from Piper betel were predicted to inhibit Ack activity. One of these Piper betel compounds found to inhibit E. coli O157:H7 growth similar to penicillin. The target specificity of these betel compounds, their effects on other studied pathogens, and other in silico results are currently being validated and the results are promising.

Original languageEnglish
Pages (from-to)495-509
Number of pages15
JournalIntegrative Biology (United Kingdom)
Volume5
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

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