Subtractive genomics study for the identification of therapeutic targets against Cronobacter sakazakii: A threat to infants
Ishtiaque Ahammad,
Anika Bushra Lamisa,
Sadia Sharmin,
Arittra Bhattacharjee,
Zeshan Mahmud Chowdhury,
Tanvir Ahamed,
Mohammad Uzzal Hossain,
Keshob Chandra Das,
Md Salimullah,
Chaman Ara Keya
Affiliations
Ishtiaque Ahammad
Bioinformatics Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, 1349, Bangladesh
Anika Bushra Lamisa
Bioinformatics Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, 1349, Bangladesh; Department of Biochemistry and Microbiology, North South University, Bashundhara, Dhaka, 1229, Bangladesh
Sadia Sharmin
Department of Biotechnology & Genetic Engineering, Jahangirnagar University, Savar, Dhaka, 1342, Bangladesh
Arittra Bhattacharjee
Bioinformatics Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, 1349, Bangladesh
Zeshan Mahmud Chowdhury
Bioinformatics Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, 1349, Bangladesh
Tanvir Ahamed
Department of Biotechnology & Genetic Engineering, Jahangirnagar University, Savar, Dhaka, 1342, Bangladesh
Mohammad Uzzal Hossain
Bioinformatics Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, 1349, Bangladesh
Keshob Chandra Das
Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, 1349, Bangladesh
Md Salimullah
Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, 1349, Bangladesh
Chaman Ara Keya
Department of Biochemistry and Microbiology, North South University, Bashundhara, Dhaka, 1229, Bangladesh; Corresponding author.
Cronobacter sakazakii is an opportunistic pathogen that has been associated with severe infection in neonates such as necrotizing enterocolitis (NEC), neonatal meningitis, and bacteremia. This pathogen can survive in a relatively dry environment, especially in powdered infant formula (PIF). Unfortunately, conventional drugs that were once effective against C. sakazakii are gradually losing their efficacy due to rising antibiotic resistance. In this study, a subtractive genomic approach was followed in order to identify potential therapeutic targets in the pathogen. The whole proteome of the pathogen was filtered through a step-by-step process, which involved removing paralogous proteins, human homologs, sequences that are less essential for survival, proteins with shared metabolic pathways, and proteins that are located in cells other than the cytoplasmic membrane. As a result, nine novel drug targets were identified. Further, the analysis also unveiled that the FDA-approved drug Terbinafine can be repurposed against the Glutathione/l-cysteine transport system ATP-binding/permease protein CydC of C. sakazakii. Moreover, molecular docking and dynamics studies of Terbinafine and CydC suggested that this drug can be used to treat C. sakazakii infection in neonates. However, for clinical purposes further in vitro and in vivo studies are necessary.
