Identification of putative non-host essential genes and novel drug targets against Acinetobacter baumannii by in silico comparative genome analysis. (March 2019)

• Record Type: Journal Article
• Authors: Uddin, Reaz; Masood, Fareha; Azam, Syed Sikander; Wadood, Abdul
• Is Part Of: Microbial pathogenesis. Volume 128(2019)
• Page Start: 28
• Page End: 35
• Publication Date: 2019-03
• Subjects: Comparative genomics -- Acinetobacter baumannii -- Docking -- Drug resistant -- Genomics; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2018.12.015
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Acinetobacter baumannii, the gram-negative bacteria emerged as an extremely critical pathogen causing nosocomial and different kinds of infections . A. baumannii exhibit resistivity towards various classes of antibiotics that shows that there is a dire need to search more drug targets by exploiting the full genome of the bacteria. In doing so, a strategy is made with the combination of computational biology, pathogen informatics and cheminformatics. Comparative genomics analysis, modeling and docking studies have been performed for the prediction of non-host essential genes and novel drug candidates against A. baumannii . Among 37 unique and 82 common metabolic pathways, 92 genes were predicted as non-host genes. Similarly, using homology search between A. baumannii genome and essential genes of different bacteria, 293 genes were predicted as essential genes of A. baumannii . Among these predicted non-host and essential genes, 86 genes were predicted as non-host essential genes which could serve as potential novel drug and vaccine targets. Additional drug-target like physicochemical properties were estimated such as the molecular weight, subcellular localization and druggability potential. On the structural part, the crystal structures of all the non-host essential genes of A. baumannii were found except the three genes. Out of these three, a homology model of Undecaprenyl-diphosphatase was built using a PDB template by MODELLER [version 9.18]. The quality of the model was assessed by the ProSA and RAMPAGE. The built model was subjected as a receptor for the molecular docking with Adenosine diphosphate (ADP) as a ligand. The molecular docking was performed by AutoDock4 and the best conformation with lowest binding energy (−4.39 kcal/mol) was obtained. The LigPlot was used to identify the close interactions between the ligand the receptor's residues. This study will further aid for the selection of putative inhibitors against a novel drug target identified against A. baumannii and hence could lead to the better therapeutics. Graphical abstract: Image 1 Highlights: Computational Subtractive Genomics analysis of completed proteomes of Acinetobacter baumannii . Metabolic Pathways analysis of core proteomic data of Acinetobacter baumannii . Potential drug targets prioritization against Acinetobacter baumannii . Protein-Ligand Interaction studies of the potential drug target against Acinetobacter baumannii .