Identification of novel non-homologous drug targets against Acinetobacter baumannii using subtractive genomics and comparative metabolic pathway analysis. (March 2021)

• Record Type: Journal Article
• Authors: Kaur, Harpreet; Kalia, Manmohit; Taneja, Neelam
• Is Part Of: Microbial pathogenesis. Volume 152(2021)
• Publication Date: 2021-03
• Subjects: Subtractive genomics -- Comparative metabolic pathway -- Drug targets -- Acinetobacter baumannii; 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.2020.104608
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Lack of effective antibiotics and the development of multidrug resistance in clinical isolates of nosocomial pathogen Acinetobacter baumanni has necessitated the identification of novel drug targets. The study is divided into three phases, in phase I, four different sets of proteins were subjected to a chokepoint, plasmid, resistance genes, and virulence factors analysis. After phase 1 analysis we obtained two hundred twenty-two proteins which were analyzed further in the phase II for essentiality and homology. Fifty-eight proteins identified as target candidates were studied for qualitative characteristics. Among them, 32 were identified as cytoplasmic membrane, 17 as cytoplasmic, one as periplasmic, one as outer membrane, two as extracellular, and location of 5 was not known. Druggability analysis revealed that 18 proteins were druggable, and 40 were novel. Drug targets obtained in the present study can be utilized for the identification of novel antimicrobials for the treatment of infections caused by multidrug-resistant A. baumannii . Predicted drug targets can be evaluated for their binding affinity by molecular docking studies and thus accelerating the process of drug discovery. Highlights: Comparative and subtractive genomics were used for shortlisting proteins as probable drug targets against A.baumanni . Targets selected on basis of essentiality, non-homology to the human host, presence in drug bank, and subcellular location. After screening of 222 proteins 18 were found druggable and 40 were found to be novel. Unique drug targets (BfmRS, kdsA, kdsB) were identified for designing new antimicrobial agents against A. baumannii .