Programa de Pós-graduação em Biologia Celular e Molecular Aplicada à Saúde,Universidade Luterana do Brasil,Canoas,Rio Grande do Sul,Brazil.
Centro de Desenvolvimento Científico e Tecnológico (CDCT),Secretaria Estadual da Saúde do Rio Grande do Sul,Porto Alegre,Rio Grande do Sul,Brazil.
Epidemiol Infect. 2019 Jan;147:e216. doi: 10.1017/S0950268819001006.
Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.
结核病（TB）是全球传染病死亡的主要原因。在估计的耐药结核病病例中，约 60%发生在金砖国家（巴西、俄罗斯、印度、中国和南非）。在巴西各州中，原发性和获得性耐多药结核病（MDR-TB）发病率最高的是南里奥格兰德州（RS）。本研究旨在对巴西高负担州 RS 州的 MDR-TB 进行分子特征分析。我们对 RS 州的 MDR-TB 病例进行了分子特征分析，这些病例是通过药敏试验定义的，使用了来自中央实验室的 131 株结核分枝杆菌（M.tb）DNA 样本。我们进行了 MIRU-VNTR 24 位、 spoligotyping、katG、inhA 和 rpoB 基因测序以及 RDRio 亚谱系鉴定。最常见的家族是 LAM（65.6%）和 Haarlem（22.1%）。在 42 株（32%）M.tb 分离株中观察到 RDRio 缺失。在 MDR-TB 病例中，有 8 例（6.1%）未在研究基因中发现突变。在 116 株（88.5%）M.tb 分离株中，我们发现了 rpoB 基因中与利福平（RIF）耐药相关的突变，在 112 株分离株（85.5%）中，我们观察到 katG 和 inhA 基因中与异烟肼耐药相关的突变。在 131 株分离株中的 19 株（19/131）中发现 rpoB 基因 516 密码子处的 12 个核苷酸（CCAGAACAACCC）插入，可能导致 RIF 和 RNA 聚合酶的相互作用降低，这些分离株主要属于 LAM 和 Haarlem 家族。这些结果有助于更好地了解该地区 MDR-TB 的传播和进化动态。
