Escherichia coli Sequence Type 410 Is Causing New International High-Risk Clones.
Escherichia coli Sequence Type 410 Is Causing New International High-Risk Clones.
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DOI：
10.1128/msphere.00337-18
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发表时间：
2018-07-18
期刊：
影响因子：
4.8
通讯作者：
Hasman H
中科院分区：
文献类型：
--
作者：
Roer L;Overballe-Petersen S;Hansen F;Schønning K;Wang M;Røder BL;Hansen DS;Justesen US;Andersen LP;Fulgsang-Damgaard D;Hopkins KL;Woodford N;Falgenhauer L;Chakraborty T;Samuelsen Ø;Sjöström K;Johannesen TB;Ng K;Nielsen J;Ethelberg S;Stegger M;Hammerum AM;Hasman H
肠外致病性大肠埃希菌（ExPEC）是引起尿路感染和败血症的主要原因。ExPEC序列类型ST 131受到了极大的关注，其被归类为“高风险”克隆。高风险克隆是全球分布的克隆，与各种抗生素耐药性决定因素，易于传播，在宿主中持久存在，以及宿主之间的有效传播有关。高风险克隆具有增强的致病性，并导致严重和/或复发性感染。我们表明，大肠杆菌ST 410谱系的克隆持续存在和/或导致人类复发性感染，包括血液感染。我们发现证据表明，ST 410是一种高度耐药的全球分布谱系，能够在患者之间传播，导致医院爆发。我们的分析表明，ST 410谱系应被归类为有可能导致新的高风险克隆。因此，随着过去几十年的克隆扩张和对最后手段治疗方案的抗生素耐药性增加，ST 410需要进行前瞻性监测。大肠埃希菌序列型410（ST 410）是一种肠外病原体，与氟喹诺酮类、第三代头孢菌素和碳青霉烯类耐药相关。在本研究中，我们调查了来自丹麦患者的ST 410大肠杆菌分离株的全国流行病学。此外，在全球范围内研究了大肠埃希菌ST 410，以进一步了解该成功谱系的碳青霉烯酶基因blaOXA-181和blaNDM-5的获得。从127个全基因组测序的分离株中，我们重建了大肠杆菌ST 410的进化框架，该框架描绘了抗生素耐药分支B2/H24 R，B3/H24 Rx和B4/H24 RxC。B2/H24 R和B3/H24 Rx进化枝在1987年左右出现，与大肠杆菌ST 131中的C1/H30 R和C2/H30 Rx进化枝同时出现。B3/H24 Rx似乎是通过获得超广谱β-内酰胺酶（ESBL）编码基因blaCTX-M-15和编码IncFIA和IncFIB的IncFIB质粒而进化的。大约在2003年，当ST 410获得携带blaOXA-181碳青霉烯酶基因的IncX 3质粒时，出现了碳青霉烯耐药分支B4/H24 RxC。2014年左右，进化枝B4/H24 RxC在保守的IncPII质粒上获得了第二个碳青霉烯酶基因blaNDM-5。通过对来自丹麦患者的49株大肠杆菌ST 410分离株的流行病学调查，我们确定了5起可能的区域性暴发，其中一起暴发涉及9名携带blaOXA-181和blaNDM-5的B4/H24 RxC分离株的患者。在过去的二十年中，大肠杆菌ST 410中积累的多药耐药性，以及其已被证明的患者之间传播的潜力，在临床环境中构成了高风险，因此，大肠杆菌ST 410应被视为具有新兴“高风险”克隆的谱系，未来应密切监测。重要性肠外致病性大肠杆菌（ExPEC）是尿路感染和败血症的主要原因。ExPEC序列类型ST 131受到了极大的关注，其被归类为“高风险”克隆。高风险克隆是全球分布的克隆，与各种抗生素耐药性决定因素，易于传播，在宿主中持久存在，以及宿主之间的有效传播有关。高风险克隆具有增强的致病性，并导致严重和/或复发性感染。我们表明，大肠杆菌ST 410谱系的克隆持续存在和/或导致人类复发性感染，包括血液感染。我们发现证据表明，ST 410是一种高度耐药的全球分布谱系，能够在患者之间传播，导致医院爆发。我们的分析表明，ST 410谱系应被归类为有可能导致新的高风险克隆。因此，随着过去几十年的克隆扩张和对最后手段治疗方案的抗生素耐药性增加，ST 410需要进行前瞻性监测。
Extraintestinal pathogenic Escherichia coli (ExPEC) is the main cause of urinary tract infections and septicemia. Significant attention has been given to the ExPEC sequence type ST131, which has been categorized as a “high-risk” clone. High-risk clones are globally distributed clones associated with various antimicrobial resistance determinants, ease of transmission, persistence in hosts, and effective transmission between hosts. The high-risk clones have enhanced pathogenicity and cause severe and/or recurrent infections. We show that clones of the E. coli ST410 lineage persist and/or cause recurrent infections in humans, including bloodstream infections. We found evidence of ST410 being a highly resistant globally distributed lineage, capable of patient-to-patient transmission causing hospital outbreaks. Our analysis suggests that the ST410 lineage should be classified with the potential to cause new high-risk clones. Thus, with the clonal expansion over the past decades and increased antimicrobial resistance to last-resort treatment options, ST410 needs to be monitored prospectively. Escherichia coli sequence type 410 (ST410) has been reported worldwide as an extraintestinal pathogen associated with resistance to fluoroquinolones, third-generation cephalosporins, and carbapenems. In the present study, we investigated national epidemiology of ST410 E. coli isolates from Danish patients. Furthermore, E. coli ST410 was investigated in a global context to provide further insight into the acquisition of the carbapenemase genes blaOXA-181 and blaNDM-5 of this successful lineage. From 127 whole-genome-sequenced isolates, we reconstructed an evolutionary framework of E. coli ST410 which portrays the antimicrobial-resistant clades B2/H24R, B3/H24Rx, and B4/H24RxC. The B2/H24R and B3/H24Rx clades emerged around 1987, concurrently with the C1/H30R and C2/H30Rx clades in E. coli ST131. B3/H24Rx appears to have evolved by the acquisition of the extended-spectrum β-lactamase (ESBL)-encoding gene blaCTX-M-15 and an IncFII plasmid, encoding IncFIA and IncFIB. Around 2003, the carbapenem-resistant clade B4/H24RxC emerged when ST410 acquired an IncX3 plasmid carrying a blaOXA-181 carbapenemase gene. Around 2014, the clade B4/H24RxC acquired a second carbapenemase gene, blaNDM-5, on a conserved IncFII plasmid. From an epidemiological investigation of 49 E. coli ST410 isolates from Danish patients, we identified five possible regional outbreaks, of which one outbreak involved nine patients with blaOXA-181- and blaNDM-5-carrying B4/H24RxC isolates. The accumulated multidrug resistance in E. coli ST410 over the past two decades, together with its proven potential of transmission between patients, poses a high risk in clinical settings, and thus, E. coli ST410 should be considered a lineage with emerging “high-risk” clones, which should be monitored closely in the future. IMPORTANCE Extraintestinal pathogenic Escherichia coli (ExPEC) is the main cause of urinary tract infections and septicemia. Significant attention has been given to the ExPEC sequence type ST131, which has been categorized as a “high-risk” clone. High-risk clones are globally distributed clones associated with various antimicrobial resistance determinants, ease of transmission, persistence in hosts, and effective transmission between hosts. The high-risk clones have enhanced pathogenicity and cause severe and/or recurrent infections. We show that clones of the E. coli ST410 lineage persist and/or cause recurrent infections in humans, including bloodstream infections. We found evidence of ST410 being a highly resistant globally distributed lineage, capable of patient-to-patient transmission causing hospital outbreaks. Our analysis suggests that the ST410 lineage should be classified with the potential to cause new high-risk clones. Thus, with the clonal expansion over the past decades and increased antimicrobial resistance to last-resort treatment options, ST410 needs to be monitored prospectively.