Anatomy of an extensively drug-resistant Klebsiella pneumoniae outbreak in Tuscany, Italy.
Anatomy of an extensively drug-resistant Klebsiella pneumoniae outbreak in Tuscany, Italy.
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DOI：
10.1073/pnas.2110227118
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发表时间：
2021-11-30
影响因子：
11.1
通讯作者：
Docquier JD
中科院分区：
文献类型：
--
作者：
Martin MJ;Corey BW;Sannio F;Hall LR;MacDonald U;Jones BT;Mills EG;Harless C;Stam J;Maybank R;Kwak Y;Schaufler K;Becker K;Hübner NO;Cresti S;Tordini G;Valassina M;Cusi MG;Bennett JW;Russo TA;McGann PT;Lebreton F;Docquier JD
耐碳青霉烯类肺炎克雷伯菌属于世界卫生组织确定的“关键优先级”细菌病原体。新兴的“高风险”谱系导致了全球范围内难以治疗的医院获得性感染和疫情暴发。通过整合 20 个月内收集的分离株的基因组和流行病学数据，这项研究揭示了意大利肺炎克雷伯菌 ST-147 的高区域流行率和在一家医院内的快速传播。除了对几乎所有抗生素具有抗性外，该谱系还携带一种混合质粒，其中含有一组先前与超毒力相关的生物标记基因。耐药性和毒力决定因素的融合是一个主要问题，这些发现强调需要进行强有力的全球监测来监测高风险肺炎克雷伯菌的出现。产生新德里金属-β-内酰胺酶 (NDM) 的耐碳青霉烯类肺炎克雷伯菌于 2018 年 11 月在意大利托斯卡纳开始长期暴发，并持续到 2020 年直至 2021 年。为了了解随时间推移的区域出现和传播动态，我们收集了 117 种广泛耐药、产生 NDM 的肺炎克雷伯菌分离株，并对其进行了基因组测序，这些分离株是在 20 个月的时间内培养的。托斯卡纳东南部多个医疗机构有 76 名患者。所有分离株均属于高风险克隆 ST-147，通常对所有一线抗生素不敏感。尽管是零星的，但由于重复的独立突变，也观察到对粘菌素、替加环素和磷霉素的耐药性。基因组分析显示，在托斯卡纳流行的 ST-147 分离株是单系的，并且具有高度遗传相关性（包括来自同一家医院的 42 名患者组成的网络，并且共享几乎相同的分离株），并且与来自中东的临床分离株共享一个最近的祖先。虽然 blaNDM-1 基因由 IncFIB 型质粒携带，但我们的研究表明，来自意大利的 ST-147 谱系还获得了一种混合 IncFIB/IncHIB 型质粒，携带 16S 甲基转移酶 armA 基因以及高毒力分离株中常见的关键毒力生物标志物。该质粒与全球流通的嵌合质粒（包括 ST-11 和 ST-307 趋同谱系）具有广泛的同源性。从表型上看，这种杂交质粒的携带导致铁载体产量增加，但在免疫活性 CD1 小鼠皮下感染模型中，其毒力并未达到典型高毒力肺炎克雷伯菌的水平。我们的研究结果强调了进行基因组监测以识别新出现的威胁的重要性。
Carbapenem-resistant Klebsiella pneumoniae belongs to the “critical-priority” tier of bacterial pathogens as identified by the World Health Organization. Emerging “high-risk” lineages are responsible for difficult-to-treat, hospital-acquired infections and outbreaks around the globe. By integrating genomic and epidemiological data for isolates collected over 20 mo, this study revealed both the high, regional prevalence and the rapid spread, within a single hospital, of K. pneumoniae ST-147 in Italy. Besides resistance to nearly all antibiotics, this lineage carried a hybrid plasmid harboring a set of biomarker genes previously linked to hypervirulence. Convergence of resistance and virulence determinants is a major concern and these findings highlight the need for robust, global surveillance to monitor the emergence of high-risk K. pneumoniae. A protracted outbreak of New Delhi metallo-β-lactamase (NDM)–producing carbapenem-resistant Klebsiella pneumoniae started in Tuscany, Italy, in November 2018 and continued in 2020 and through 2021. To understand the regional emergence and transmission dynamics over time, we collected and sequenced the genomes of 117 extensively drug-resistant, NDM-producing K. pneumoniae isolates cultured over a 20-mo period from 76 patients at several healthcare facilities in southeast Tuscany. All isolates belonged to high-risk clone ST-147 and were typically nonsusceptible to all first-line antibiotics. Albeit sporadic, resistances to colistin, tigecycline, and fosfomycin were also observed as a result of repeated, independent mutations. Genomic analysis revealed that ST-147 isolates circulating in Tuscany were monophyletic and highly genetically related (including a network of 42 patients from the same hospital and sharing nearly identical isolates), and shared a recent ancestor with clinical isolates from the Middle East. While the blaNDM-1 gene was carried by an IncFIB-type plasmid, our investigations revealed that the ST-147 lineage from Italy also acquired a hybrid IncFIB/IncHIB–type plasmid carrying the 16S methyltransferase armA gene as well as key virulence biomarkers often found in hypervirulent isolates. This plasmid shared extensive homologies with mosaic plasmids circulating globally including from ST-11 and ST-307 convergent lineages. Phenotypically, the carriage of this hybrid plasmid resulted in increased siderophore production but did not confer virulence to the level of an archetypical, hypervirulent K. pneumoniae in a subcutaneous model of infection with immunocompetent CD1 mice. Our findings highlight the importance of performing genomic surveillance to identify emerging threats.
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影响因子：
16.6
作者：
Lam MMC;Wick RR;Watts SC;Cerdeira LT;Wyres KL;Holt KE
通讯作者：
Holt KE
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影响因子：
3.1
作者：
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Van Tyne D
影响因子：
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作者：
Basavanna S;Chimalapati S;Maqbool A;Rubbo B;Yuste J;Wilson RJ;Hosie A;Ogunniyi AD;Paton JC;Thomas G;Brown JS
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影响因子：
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作者：
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通讯作者：
Bitar I