In Silico Analysis of S315T and S315R Mutations of Multidrug-resistant Mycobacterium tuberculosis Clinical Isolates from Karachi, Pakistan (original) (raw)

Background: Tuberculosis is one of the most frequent and persistent global diseases causing millions of deaths every year. Pakistan lies at number 6 among the 22 most dominant countries, with multidrug resistance up to 15%. Isoniazid-resistant strains of Mycobacterium tuberculosis are gradually rising and seem to be more prevalent in developing countries. Mutations in the katG gene are considered to be responsible for the accusation of isoniazid resistance in M. tuberculosis. Objectives: The current study was designed to investigate the structural and functional associations of KatG gene mutations (S315R and S315T) and multidrug resistance in M. tuberculosis isolates from Karachi, Pakistan. Results: The present study revealed conformational changes in the structure of the KatG enzyme due to observed mutations, which led to induced alterations in isoniazid binding residues at the active site of the KatG enzyme. Furthermore, substantial changes were observed in interaction energy, lig...