01528nas a2200205   4500000000100000008004100001653002500042653002500067653002300092653001500115653002800130100001600158700001500174700001500189700001300204245012300217300000800340520096000348022001401308       2017                            d10aQuinolone resistance10aMycobacterium leprae10aEnzymatic activity10aDNA gyrase10aAmino Acid Substitution1 aYamaguchi T1 aYokoyama K1 aNakajima C1 aSuzuki Y00aQuinolone resistance-associated amino acid substitutions affect enzymatic activity of Mycobacterium leprae DNA gyrase.  a1-53 a<p>Quinolones are important antimicrobials for treatment of leprosy, a chronic infectious disease caused by Mycobacterium leprae. Although it is well known that mutations in DNA gyrase are responsible for quinolone resistance, the effect of those mutations on the enzymatic activity is yet to be studied in depth. Hence, we conducted in vitro assays to observe supercoiling reactions of wild type and mutated M. leprae DNA gyrases. DNA gyrase with amino acid substitution Ala91Val possessed the highest activity among the mutants. DNA gyrase with Gly89Cys showed the lowest level of activity despite being found in clinical strains, but it supercoiled DNA like the wild type does if applied at a sufficient concentration. In addition, patterns of time-dependent conversion from relaxed circular DNA into supercoiled DNA by DNA gyrases with clinically unreported Asp95Gly and Asp95Asn were observed to be distinct from those by the other DNA gyrases.</p>
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