title: 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.
abstract: 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.
authors.affiliation: Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsuoka
authors.affiliation: Department of Medical Research, Yangon, Myanmar.
authors.forename: Khin Saw
authors.initials: KS
authors.lastname: Aye
authors.affiliation: Central Special Skin Clinic, Yangon General Hospital, Yangon, Myanmar.
authors.forename: Kyaw
authors.initials: K
authors.lastname: Kyaw
authors.affiliation: Leonard Wood Memorial, Cebu, The Philippines.
authors.forename: Esterlina Virtudes
authors.initials: EV
authors.lastname: Tan
authors.affiliation: Leonard Wood Memorial, Cebu, The Philippines.
authors.forename: Ma Victoria
authors.initials: MV
authors.lastname: Balagon
authors.affiliation: Leonard Wood Memorial, Cebu, The Philippines.
authors.forename: Paul
authors.initials: P
authors.lastname: Saunderson
authors.affiliation: Leonard Wood Memorial, Cebu, The Philippines.
authors.forename: Robert
authors.initials: R
authors.lastname: Gelber
authors.affiliation: National Leprosy Hospital Okukomyoen, Okayama, Japan.
authors.forename: Masanao
authors.initials: M
authors.lastname: Makino
authors.affiliation: Department of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Nakajima
authors.affiliation: Department of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003906:Developing Countries; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007917:Leprostatic Agents / Q000494:pharmacology*; D007918:Leprosy / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D009154:Mutation; D002052:Myanmar; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010679:Philippines; D015995:Prevalence
chemical_list: D001426:Bacterial Proteins; D007917:Leprostatic Agents