Identification of novel non-homologous drug targets against Acinetobacter baumannii using subtractive genomics and comparative metabolic pathway analysis

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.