Identification of repurposable drug targets in Mycoplasma pneumoniae using subtractive genomics, molecular docking and dynamics simulation

Zeshan Mahmud Chowdhury; Tabassum Binte Jamal; Ishtiaque Ahammad; Arittra Bhattacharjee; Anika Bushra Lamisa; Jannatul Maoa Jani; Md Fahim Israk; Mohammad Uzzal Hossain; Keshob Chandra Das; Chaman Ara Keya; Md Salimullah

doi:10.1016/j.heliyon.2023.e21466

Identification of repurposable drug targets in Mycoplasma pneumoniae using subtractive genomics, molecular docking and dynamics simulation

Heliyon. 2023 Nov 4;9(11):e21466. doi: 10.1016/j.heliyon.2023.e21466. eCollection 2023 Nov.

Affiliations

¹ Bioinformatics Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, 1349, Bangladesh.
² Department of Biotechnology and Genetic Engineering, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
³ Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka, 1349, Bangladesh.
⁴ Department of Biochemistry and Microbiology, North South University, Bashundhara, Dhaka, 1229, Bangladesh.

Abstract

Mycoplasma pneumoniae is a significant causative agent of community-acquired pneumonia, causing acute inflammation in the upper and lower respiratory tract as well as extrapulmonary syndromes. In particular, the elderly and infants are at greater risk of developing severe, life-threatening pneumonia caused by M. pneumoniae. Yet, the global increase in antimicrobial resistance against antibiotics for the treatment of M. pneumoniae infection highlights the urgent need to explore novel drug targets. To this end, bioinformatics approaches, such as subtractive genomics, can be employed to identify specific metabolic pathways and essential proteins unique to the pathogen that could be potential targets for new drugs. In this study, we implemented a subtractive genomics approach to identify 61 metabolic pathways and 42 essential proteins that are unique to M. pneumoniae. A subsequent screening in the DrugBank database revealed three druggable proteins with similarity to FDA-approved small-molecule drugs, and finally, the compound CHEBI:97093 was identified as a promising novel putative drug target. These findings can provide crucial insights for the development of highly effective drugs that selectively inhibit the pathogen-specific metabolic pathways, leading to better management and treatment of M. pneumoniae infections.

Keywords: Antibiotic resistance; Essential proteins; Metabolic pathway; Mycoplasma pneumoniae; Subtractive genomics.