02243nas a2200397 4500000000100000008004100001260001300042653002300055653002500078653003100103653004200134653001100176653002300187653001200210653001300222653001200235653002500247653004400272653001600316653001500332100001500347700001100362700001100373700001100384700001600395700001700411700001300428700001300441700001500454700001300469245017900482300001100661490000700672520115200679022001401831 2008 d c2008 Oct10aBacterial Proteins10aDeveloping countries10aDrug Resistance, Bacterial10aGene Expression Regulation, Bacterial10aHumans10aLeprostatic Agents10aleprosy10aMutation10aMyanmar10aMycobacterium leprae10aOligonucleotide Array Sequence Analysis10aPhilippines10aPrevalence1 aMatsuoka M1 aAye KS1 aKyaw K1 aTan EV1 aBalagon MVF1 aSaunderson P1 aGelber R1 aMakino M1 aNakajima C1 aSuzuki Y00aA novel method for simple detection of mutations conferring drug resistance in Mycobacterium leprae, based on a DNA microarray, and its applicability in developing countries. a1213-90 v573 a
A simple method to detect mutations in the genome of Mycobacterium leprae that confer resistance to key drugs for leprosy was exploited on the basis of a reverse hybridization system. A series of oligonucleotide probes corresponding to each mutation in the folP1, rpoB and gyrA genes for dapsone, rifampicin and ofloxacin resistance, respectively, were selected and fixed on a glass slide as capture probes, to develop a DNA microarray termed the leprosy drug susceptibility-DNA microarray (LDS-DA). Mutations in clinical isolates of M. leprae were successfully identified by the LDS-DA. Feasibility studies were conducted to evaluate the performance of the LDS-DA in two developing countries, Myanmar and the Philippines. The high concordance of the results obtained by this method with the results of nucleotide sequencing strongly supports the applicability of the LDS-DA as a drug susceptibility test in place of sequencing, a time-consuming and costly procedure. This is a rapid and simple method for the simultaneous susceptibility testing of three front-line drugs for leprosy, and solves the problems of previously reported methods.
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