Klebsiella pneumoniae has been implicated in wide-ranging nosocomial outbreaks, causing severe infections without effective treatments due to antibiotic resistance. Here, we performed genome sequencing of 70 extensively drug resistant clinical isolates, collected from Brasília’s hospitals (Brazil) between 2010 and 2014. The majority of strains (60 out of 70) belonged to a single clonal complex (CC), CC258, which has become distributed worldwide in the last two decades. Of these CC258 strains, 44 strains were classified as sequence type 11 (ST11) and fell into two distinct clades, but no ST258 strains were found. These 70 strains had a pan-genome size of 10 366 genes, with a core-genome size of ~4476 genes found in 95 % of isolates. Analysis of sequences revealed diverse mechanisms of resistance, including production of multidrug efflux pumps, enzymes with the same target function but with reduced or no affinity to the drug, and proteins that protected the drug target or inactivated the drug. β-Lactamase production provided the most notable mechanism associated with K. pneumoniae . Each strain presented two or three different β-lactamase enzymes, including class A (SHV, CTX-M and KPC), class B and class C AmpC enzymes, although no class D β-lactamase was identified. Strains carrying the NDM enzyme involved three different ST types, suggesting that there was no common genetic origin.

中文翻译：

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对肺炎克雷伯菌广泛耐药临床分离株多样性、毒力和耐药性的基因组学见解

肺炎克雷伯菌 已牵涉到广泛的医院爆发，由于抗生素耐药性，在没有有效治疗的情况下导致严重感染。在这里，我们对 2010 年至 2014 年间从巴西利亚的医院（巴西）收集的 70 种广泛耐药临床分离株进行了基因组测序。大多数菌株（70 株中的 60 株）属于单一克隆复合体（CC）CC258，其具有近二十年来在世界范围内分布。在这些 CC258 菌株中，44 株被归类为序列类型 11 (ST11) 并分为两个不同的进化枝，但未发现 ST258 菌株。这 70 个菌株具有 10 366 个基因的泛基因组大小，在 95% 的分离物中发现了约 4476 个基因的核心基因组大小。序列分析揭示了多种耐药机制，包括多药外排泵的产生，具有相同靶点功能但对药物亲和力降低或没有亲和力的酶，以及保护药物靶点或使药物失活的蛋白质。β-内酰胺酶的产生提供了与相关的最显着的机制 肺炎克雷伯菌 。每个菌株呈现两种或三种不同的 β-内酰胺酶，包括 A 类（SHV、CTX-M 和 KPC）、B 类和 C 类 AmpC 酶，但未鉴定出 D 类 β-内酰胺酶。携带 NDM 酶的菌株涉及三种不同的 ST 类型，表明没有共同的遗传起源。