Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, RJ, Brazil.
J Clin Microbiol. 2012 Jun;50(6):1912-7. doi: 10.1128/JCM.06561-11. Epub 2012 Apr 11.
Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P = 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary.
从巴西五个不同地区的 145 例复发麻风病例中采集皮肤活检样本，用于对与麻风分枝杆菌耐药性相关的部分基因进行序列分析。在 92 例阳性扩增病例中的 4 例（4.3%）观察到这些基因中的单核苷酸多态性（SNP），包括仅 rpoB 突变的病例、folP1 和 rpoB 中均存在 SNP 的另一个样本，以及两个 folP1、rpoB 和 gyrA 均存在突变的病例，提示存在多药耐药（MDR）。突变的性质与早期研究中报道的相同，folP 中的密码子 55 从 CCC 突变为 CGC（Pro 突变为 Arg），而 rpoB 中的所有突变均发生在密码子 531 处，其中两个突变为 TCG 突变为 ATG（Ser 突变为 Met），一个突变为 TCG 突变为 TTC（Ser 突变为 Phe），一个突变为 TCG 突变为 TTG（Ser 突变为 Leu）。gyrA 中发生突变的两个病例，其密码子 91 从 GCA 突变为 GTA（Ala 突变为 Val）。从治愈到复发诊断的中位时间为 9.45 年，但突变患者的时间明显缩短（3.26 年；P = 0.0038）。超过 70%的复发为多菌型，包括 3 例携带突变的病例；1 例 MDR 复发患者为少菌型。
