Drug target identification and virtual screening in pursuit of phytochemical intervention of Mycobacterium chelonae

Abstract

Mycobacterium chelonae is a rapidly growing mycobacterium present in the environment. It is associated with skin and soft tissue infections including abscess, cellulitis and osteomyelitis. Other infections by this bacterium are post-operative/transplant-associated, catheter, prostheses and even concomitant to haemodialytic procedures. In this study, we employ a subtractive genomics approach to predict the potential therapeutic candidates, intended for experimental research against this bacterium. A computational workflow was devised and executed to procure core proteome targets essential to the pathogen but with no similarity to the human host. Initially, essential Mycobacterium chelonae proteins were predicted through homology searching of core proteome content from 19 different bacteria. Druggable proteins were then identified and N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) was chosen as a case study from identified therapeutic targets, based on its important bifunctional role. Structure modeling was followed by virtual screening of phytochemicals (N > 10,000) against it. 4,4-[(1E)-5-hydroxy-4-(methoxymethyl)-1-pentene-1,5-diyl]diphenol, apigenin-7-O-beta-gluconopyranoside and methyl rosmarinate were screened as compounds having best potential for binding GlmU. Phytotherapy helps curb the menace of antibiotic resistance so treatment of Mycobacterium chelonae infection through this method is recommended.