Here we described phenotypical, molecular and epidemiological features of a highly rifampicin-resistant Mycobacterium tuberculosis strain emerging in Southern Brazil, that carries an uncommon insertion of 12 nucleotides at the codon 435 in the rpoB gene. Employing a whole-genome sequencing-based study on drug-resistant Mycobacterium tuberculosis strains, we identified this emergent strain in 16 (9.19%) from 174 rifampicin-resistant clinical strains, all of them belonging to LAM RD115 sublineage. Nine of these 16 strains were available to minimum inhibitory concentration determination and for all of them was found a high rifampicin-resistance level (≥to 32 mg/L). This high resistance level could be explained by structural changes into the RIF binding site of RNA polymerase caused by the insertions, and consequent low-affinity interaction with rifampicin complex confirmed through protein modeling and molecular docking simulations. Epidemiological investigation showed that most of the individuals (56.25%) infected by the studied strains were prison inmate individuals or that spent some time in prison. The phylogenomic approach revealed that strains carrying on insertion belonged to same genomic cluster, evidencing a communal transmission chain involving inmate individuals and community. We stress the importance of tuberculosis genomic surveillance and introduction of measures to interrupt Mycobacterium tuberculosis transmission chain in this region.

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巴西南部出现高度抗利福平的结核分枝杆菌菌株

在这里，我们描述了巴西南部出现的高度耐利福平结核分枝杆菌菌株的表型、分子和流行病学特征，该菌株在 rpoB 基因的密码子 435 处插入了 12 个不常见的核苷酸。通过对耐药结核分枝杆菌菌株进行基于全基因组测序的研究，我们从 174 株利福平耐药临床菌株中的 16 株（9.19%）中鉴定出这种新出现的菌株，所有菌株均属于 LAM RD115 亚系。这 16 株菌株中有 9 株可用于最低抑菌浓度测定，并且所有菌株均具有较高的利福平耐药水平（≥ 32 mg/L）。这种高抗性水平可以通过插入导致 RNA 聚合酶的 RIF 结合位点的结构变化来解释，通过蛋白质建模和分子对接模拟证实了随后与利福平复合物的低亲和力相互作用。流行病学调查显示，被研究毒株感染的大多数（56.25%）是监狱囚犯或在监狱呆过一段时间的人。系统基因组学方法表明，进行插入的菌株属于同一基因组簇，证明涉及囚犯个人和社区的公共传播链。我们强调结核病基因组监测和采取措施阻断该地区结核分枝杆菌传播链的重要性。25%) 被研究菌株感染的是监狱囚犯或在监狱中度过了一段时间的人。系统基因组学方法表明，进行插入的菌株属于同一基因组簇，证明涉及囚犯个人和社区的公共传播链。我们强调结核病基因组监测和采取措施阻断该地区结核分枝杆菌传播链的重要性。25%) 被研究菌株感染的是监狱囚犯或在监狱中度过了一段时间的人。系统基因组学方法表明，进行插入的菌株属于同一基因组簇，证明涉及囚犯个人和社区的公共传播链。我们强调结核病基因组监测和采取措施阻断该地区结核分枝杆菌传播链的重要性。