TY - JOUR KW - Bacterial Proteins KW - Developing countries KW - Drug Resistance, Bacterial KW - Gene Expression Regulation, Bacterial KW - Humans KW - Leprostatic Agents KW - leprosy KW - Mutation KW - Myanmar KW - Mycobacterium leprae KW - Oligonucleotide Array Sequence Analysis KW - Philippines KW - Prevalence AU - Matsuoka M AU - Aye KS AU - Kyaw K AU - Tan EV AU - Balagon MVF AU - Saunderson P AU - Gelber R AU - Makino M AU - Nakajima C AU - Suzuki Y AB -

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.

BT - Journal of medical microbiology C1 - http://www.ncbi.nlm.nih.gov/pubmed/18809547?dopt=Abstract DA - 2008 Oct DO - 10.1099/jmm.0.2008/002600-0 IS - Pt 10 J2 - J. Med. Microbiol. LA - eng N2 -

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.

PY - 2008 SP - 1213 EP - 9 T2 - Journal of medical microbiology TI - A novel method for simple detection of mutations conferring drug resistance in Mycobacterium leprae, based on a DNA microarray, and its applicability in developing countries. VL - 57 SN - 0022-2615 ER -