: The emergence of
multidrug resistant tuberculosis (MDRTB) highlights the urgent need to understand the mechanisms of resistance to the drugs and to develop a new arena of
therapeutics to treat the disease.
Ethambutol, isonazid,
pyrazinamide,
rifampicin are first line of drugs against TB, whereas
aminoglycoside,
polypeptides,
fluoroquinolone,
ethionamide are important second line of bactericidal drugs used to treat MDRTB, and resistance to one or both of these drugs are defining characteristic of extensively
drug resistant TB. We retrieved 1,221 resistant genes from Antibiotic Resistance Gene Database (ARDB), which are responsible for resistance against first and second line
antibiotics used in treatment of
Mycobacterium tuberculosis infection. From network analysis of these resistance genes, 53 genes were found to be common. Phylogenetic analysis shows that more than 60% of these genes code for
acetyltransferase.
Acetyltransferases detoxify
antibiotics by acetylation, this mechanism plays central role in antibiotic resistance. Seven
acetyltransferase (AT-1 to AT-7) were selected from phylogenetic analysis. Structural alignment shows that these
acetyltransferases share common ancestral core, which can be used as a template for structure based
drug designing. From STRING analysis it is found that
acetyltransferase interact with 10 different
proteins and it shows that, all these interaction were specific to M.
tuberculosis. These results have important implications in designing new therapeutic strategies with
acetyltransferase as lead co-target to combat against MDR as well as Extreme
drug resistant (XDR)
tuberculosis.
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