Phylogenetic and Structural Significance of Dihydrofolate Synthase (folC) Mutations in Drug-Resistant Mycobacterium tuberculosis
2016
The aim of this study is to investigate the mutation pattern of the folC gene in drug-resistant Mycobacterium tuberculosis (MTB) clinical isolates of global and Hong Kong
cohorts. The public
sequence read archivesof 1,124 MTB genomes from three
independent studieswere retrieved and folC mutations existing solely in drug-resistant MTB strains were identified. A phylogenetic tree was constructed to analyze the segregation of mutation-related amino acid residues in the FolC structure. These mutation sites were further supported by direct
Sanger sequencingof the folC gene among 254 clinical MTB isolates in a Hong Kong
cohort.
Homology modelingof wild-type and mutated FolC was performed, and the predicted structures were docked with hydroxydihydropteroate, the metabolic derivative of
para-aminosalicylic acid(PAS), to evaluate the resultant binding affinity changes. Combining the results of three previous
cohortsand our
cohort, E40, I43, S150, and E153 are the most frequently affected amino acid residues ...
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