Protein Therapeutic Target Candidates Against Acinetobacter baumannii, a Pathogen of Concern to Planetary Health: A Network-Based Integrative Omics Drug Discovery Approach
- 1 February 2023
- journal article
- research article
- Published by Mary Ann Liebert Inc in OMICS: A Journal of Integrative Biology
- Vol. 27 (2), 62-74
- https://doi.org/10.1089/omi.2022.0180
Abstract
Acinetobacter baumannii, an opportunistic gram-negative pathogen responsible for several nosocomial infections, has developed resistance to various antibiotics. Proteins involved in the two-component system (TCS), virulence, and antibiotic resistance (AR), help this pathogen in regulating antibiotic susceptibility and virulence mechanisms. The present study reports a network-based integrative omics approach to drug discovery to identify key regulatory proteins as therapeutic candidates against A. baumannii. We collected data on the TCS, virulence, and AR proteins from various databases (P2CS, VFDB, ARDB, and PAIDB), which were subjected to network, host–pathogen, and gene expression data analysis. Network analysis identified 43 hubs, and 10 proteins were found to be interacting with human proteins associated with vital pathways. Of the 53 (43 + 10) pathogen proteins, 46 had no orthologs in the human host. Twelve proteins, namely, RpfC, Wzc, OmpR, EnvZ, BfmS, PilG, histidine kinase, ABC 3 transport family protein, outer membrane porin OprD family, CsuD, Pgm, and LpxA, were differentially expressed in the resistant strain. We propose these proteins as key regulators that warrant evaluation as therapeutic target candidates in the future. Furthermore, structure prediction of ABC 3 transport family protein was performed as a case study. The findings from this study are poised to facilitate and inform drug discovery and development against A. baumannii.Keywords
This publication has 62 references indexed in Scilit:
- Defining and searching for structural motifs using DeepView/Swiss-PdbViewerBMC Bioinformatics, 2012
- Substrate Specificity within a Family of Outer Membrane Carboxylate ChannelsPLoS Biology, 2012
- Phosphoethanolamine Modification of Lipid A in Colistin-Resistant Variants of Acinetobacter baumannii Mediated by the pmrAB Two-Component Regulatory SystemAntimicrobial Agents and Chemotherapy, 2011
- P2CS: a database of prokaryotic two-component systemsNucleic Acids Research, 2010
- HPIDB - a unified resource for host-pathogen interactionsBMC Bioinformatics, 2010
- PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotesBioinformatics, 2010
- ARDB--Antibiotic Resistance Genes DatabaseNucleic Acids Research, 2008
- UniProt: the Universal Protein knowledgebaseNucleic Acids Research, 2004
- Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction NetworksGenome Research, 2003
- Predicting transmembrane protein topology with a hidden markov model: application to complete genomesJournal of Molecular Biology, 2001