In silico Identification of Novel Common Drug Targets Against Four Infectious Acinetobacter Species

Abstract

The global emergence of multidrug-resistant Acinetobacter species has become a major concern in the management of hospital-acquired infections. Moreover, misdiagnosis of one species of Acinetobacter with another has been reported, making it difficult to choose appropriate treatment. World Health Organization emphasizes the urgent need to develop new antibiotics to combat Acinetobacter infections. This study aimed to discover novel common drug targets that will be effective against Acinetobacter nosocomialis, Acinetobacter baumannii, Acinetobacter pittii, and Acinetobacter haemolyticus. We utilized a cluster-based subtractive genomics approach to identify potential drug targets. The main focus was to find drug targets that are absent in humans and essential for pathogens. We also performed metabolic pathway and subcellular localization analyses. Furthermore, protein structure-based studies and druggability analyses were conducted to identify viable therapeutic options. Out of 1245 protein clusters (minimum 4 proteins/cluster), 204 clusters were human non-homologous and essential for bacteria. Among them, 39 clusters were cytoplasmic and involved in unique metabolic pathways which are specific to the pathogens. After analyzing the drug target sequences of DrugBank database, 12 clusters were found to be novel drug targets. Eventually, proteins of one cluster were identified as advantageous drug targets having drug-binding pockets at very similar regions with high druggability scores. These proteins can be inhibited to disrupt the Lysine/DAP biosynthetic pathway of Acinetobacter. Our research might open up a new possibility for drug discovery against these pathogens.