Detection of drug-resistance associated mutations in patients with recurring or treatment-resistant leprosy during 2010-2011

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Author:
TIAN Wei-wei(Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China)
SHEN Jian-ping(Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China)
YU Mei-wen(Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China)
YAN Liang-bin(Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China)
ZHANG Guo-cheng(Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China)
ZHOU Min(Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China)
WANG Hong-sheng(Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China)
Journal Title:
Chinese Journal of Dermatology
Issue:
Volume 45, Issue 09, 2012
DOI:
10.3760/cma.j.issn.0412-4030.2012.09.004
Key Word:
Leprosy; Drug tolerance; Genes; Mutation; Recurrence

Abstract: Objective To detect gene mutations associated with dapsone-,rifampicin-and ofloxacinresistance in lesions of patients with recurring or treatment-resistant leprosy collected from 2010 to 2011.Methods Clinical data and lesional specimens were collected during 2010-2011 from patients with recurring or treatment-resistant leprosy who were diagnosed and reported by provincial centers for leprosy control.Mycobacterium leprae DNA was extracted from the specimens and subjected to PCR for the amplification of folP1,rpoB and gyrA genes.The PCR products were directly sequenced and BLAST program was used to compare the sequence of isolated strains with the reference sequence in GenBank.Results Twenty-four patients were enrolled in this study,including 13 with recurring leprosy and 11 with treatment-resistant leprosy.Twenty-one patients showed positive PCR results in all the three regions.Of these PCR-positive specimens,3 from 1 patient with recurring and 2 patients with resistant leprosy harbored a point mutation,acc (threonine)→gcc (alanine),at codon 53 in the floP1 gene,1 from a patient with recurring leprosy harbored a missense mutation,gat (aspartic acid) → aac (asparagine),at codon 441 in the rpoB gene.Conclusions Mutations are detected in the folP1 and rpoB genes,which are associated with the resistance to dapsone and rifampicin respectively,but not in the ofloxacin resistance-associated gyrA gene,in Mycobacterium leprae isolates from patients with recurring or treatment-resistant leprosy.

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