Convergence and global epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc 3 virulence locus
Convergence and global epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc 3 virulence locus
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携带 iuc 3 毒力位点的肺炎克雷伯菌质粒的趋同和全球流行病学
DOI：
10.1101/2024.01.05.574329
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Gibbon M
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文献类型：
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作者：
Gibbon M
肺炎克雷伯菌是人类和动物的重要病原体，近年来发现的同时携带毒力基因和抗菌素耐药基因(ARGs)的“聚合型”菌株引起了严重的公共卫生关注。编码铁载体需氧肌动蛋白的质粒-Borneucocus是该物种的关键毒力因子。Variantiuc3与猪和人临床分离株相关，主要由非特异性INCF质粒携带。方法我们使用短读和长读测序相结合的方法来鉴定79株KP分离株和Onek携带IncFIB(K)/IncFIIiuc3的质粒。催产素在意大利(SPARK)和泰国(OH-DART)的两项大型“One-Health”研究中被发现。添加来自公共资料库的数据，得到了517iuc3分离株的组合数据集，并使用聚类和系统发育方法对质粒进行了分析。发现我们注意到来自泰国的7个大的、聚合的质粒，它们是通过共循环质粒harbringiuc3和编码超广谱β-内酰胺酶(ESBLS)的抗菌素耐药基因(ARGs)杂交而产生的。我们还能够鉴定出与邻近的两个肉类市场大部分相关的推测亲本质粒，就像杂交质粒一样。聚类和全球系统发育分析解决了在亚洲流行的一个iuc3质粒亚组，偶尔在欧洲和其他地方也有例子。这种变异体携带多个ARG，通常由临床分离株携带，因此需要有针对性的质粒监测。说明我们的研究表明，导致耐药性和毒力特征趋同的质粒杂交可能非常常见，即使在非临床(One-Health)环境中。种群规模的质粒基因组学使识别假定的亲本质粒成为可能，这将有助于识别最有可能杂交的质粒型，以及对质粒和宿主可能产生的选择后果。一种独特的3质粒亚型与亚洲的临床分离株相关，需要密切监测。研究背景最近发表了多篇关于肺炎克雷伯菌同时具有超强毒力和多药耐药的聚合克隆(mdr-hvKp)的报道；2023年11月的PubMed检索到的关键词是聚合肺炎克雷伯菌，共检索到143篇论文，其中99篇发表于2020年以后。我们的研究表明，携带AMR和毒力基因的质粒的杂交在自然种群中是一个频繁的、持续的过程。因此，随后携带这两种特性的质粒的转移很可能是融合菌株传播的关键驱动因素。我们的研究还提供了杂交组装如何促进大规模全球基因组质粒流行病学的范例。研究之前的证据尽管最近的多份报告强调了收敛的KP菌株的出现和传播，但同一质粒内的抗性和毒力基因的融合还没有在种群水平上进行研究，而且很少识别出假定的亲本质粒。此外，在全球范围内使用长读和短读数据对密切相关的质粒进行高分辨率基因组流行病学研究的很少。附加值我们将可用于质粒的完整序列的数量增加了一倍以上，从58到139，并提供了关于最有可能容纳这些质粒的宿主谱系(例如ST35)和流行病学来源(例如猪、野生动物、人类)的证据。我们对…系统发育和聚类的比较分析
BackgroundKlebsiella pneumoniae(Kp) is an important pathogen of humans and animals, and recent reports of ‘convergent’ strains that carry both virulence and antimicrobial resistance genes (ARGs) have raised serious public health concern. The plasmid-borneiuclocus, encoding the siderophore aerobactin, is a key virulence factor in this species. The variantiuc3 is associated with porcine and human clinical isolates and is carried by mostly uncharacterised IncF plasmids.MethodsWe used a combination of short-read and long-read sequencing to characterise IncFIB(K)/IncFIIiuc3-carrying plasmids harboured by 79 Kp isolates and oneK. oxytocaisolate recovered as part of two large ‘One-Health’ studies in Italy (SpARK) and Thailand (OH-DART). Adding data from public repositories gave a combined dataset of 517iuc3 isolates, and the plasmids were analysed using both clustering and phylogenetic methods.FindingsWe note seven large, convergent, plasmids from Thailand that have emerged through the hybridisation of co-circulating plasmids harbouringiuc3 and antimicrobial resistance genes (ARGs) encoding extended-spectrum beta-lactamases (ESBLs). We were also able to identify putative parental plasmids which were mostly associated with two neighbouring meat markets, as were the hybrid plasmids. Clustering and global phylogenetic analyses resolved aniuc3 plasmid sub-group circulating throughout Asia, with occasional examples in Europe and elsewhere. This variant carries multiple ARGs and is commonly harboured by clinical isolates, thus warranting targeted plasmid surveillance.InterpretationOur study reveals that plasmid hybridisation leading to the convergence of resistance and virulence traits may be very common, even in non-clinical (‘One-Health’) settings. Population-scale plasmid genomics makes it possible to identify putative parental plasmids, which will help to identify plasmid types that are most likely to hybridise, and what the selective consequences may be for the plasmid and host. A distinctiuc3 plasmid sub-variant is associated with clinical isolates in Asia which requires close monitoring.Research In ContextMultiple reports of ‘convergent’ clones ofKlebsiella pneumoniaethat combine both hypervirulence and multidrug resistance (MDR-hvKp) have been published recently; a PubMed search in November 2023 using the key words ‘convergenceKlebsiella pneumoniae’ returned 143 papers, 99 of which were published from 2020 onwards. Our study demonstrates that the hybridisation of plasmids carrying AMR and virulence genes is a frequent, ongoing, process in natural populations. The subsequent transfer of plasmids conferring both traits is thus likely to be a key driver behind the spread of convergent strains. Our study also provides an exemplar of how hybrid assemblies can facilitate large-scale global genomic plasmid epidemiology.Evidence before the studyAlthough multiple recent reports highlight the emergence and spread of convergent Kp strains, the confluence of resistance and virulence genes within the same plasmid has not been studied at a population level, and putative parental plasmids are rarely identified. Moreover, there have been few high-resolution genomic epidemiology studies on closely related plasmids using both long and short-read data on a global scale.Added valueWe more than double the number of complete sequences available for plasmids harbouringiuc3 from 58 to 139 and provide evidence on the host lineages most likely to harbour these plasmids (e.g., ST35), and epidemiological source (e.g., pig, wild animal, human). Our comparative analysis of phylogenetic and clustering …