Hetland Marit A K, Winkler Mia A, Kaspersen Håkon P, Håkonsholm Fredrik, Bakksjø Ragna-Johanne, Bernhoff Eva, Delgado-Blas Jose F, Brisse Sylvain, Correia Annapaula, Fostervold Aasmund, Lam Margaret M C, Lunestad Bjørn-Tore, Marathe Nachiket P, Raffelsberger Niclas, Samuelsen Ørjan, Sunde Marianne, Sundsfjord Arnfinn, Urdahl Anne Margrete, Wick Ryan R, Löhr Iren H, Holt Kathryn E
Department of Medical Microbiology, Stavanger University Hospital, Stavanger, Norway.
Department of Biological Sciences, Faculty of Science and Technology, University of Bergen, Bergen, Norway.
Genome Med. 2025 Apr 28;17(1):42. doi: 10.1186/s13073-025-01466-0.
Members of the Klebsiella pneumoniae species complex (KpSC) are opportunistic pathogens that cause severe and difficult-to-treat infections. KpSC are common in non-human niches, but the clinical relevance of these populations is disputed.
In this study, we analysed 3255 whole-genome sequenced isolates from human, animal and marine sources collected in Norway between 2001 and 2020. We used population genomics in a One Health context to assess the diversity of strains, genes and other clinically relevant genetic features within and between sources. We further explored niche-enriched traits using genome-wide association studies and investigated evidence of spillover and connectivity across the KpSC populations from the three niches.
We found that the KpSC populations in different niches were distinct but overlapping. Overall, there was high genetic diversity both between and within sources, with nearly half (49%) of the genes in the accessory genome overlapping the ecological niches. Further, several sublineages (SLs) including SL17, SL35, SL37, SL45, SL107 and SL3010 were common across sources. There were few niche-enriched traits, except for aerobactin-encoding plasmids and the bacteriocin colicin a, which were associated with KpSC from animal sources. Human infection isolates showed the greatest connectivity with each other, followed by isolates from human carriage, pigs, and bivalves. Nearly 5% of human infection isolates had close relatives (≤22 substitutions) amongst animal and marine isolates, despite temporally and geographically distant sampling of these sources. There were limited but notable recent spillover events, including the movement of plasmids encoding the virulence locus iuc3 between pigs and humans.
Our large One Health genomic study highlights that human-to-human transmission of KpSC is more common than transmission between ecological niches. Still, spillover of clinically relevant strains and genetic features between human and non-human sources does occur and should not be overlooked. Infection prevention measures are essential to limit transmission within human clinical settings and reduce infections. However, preventing transmission that leads to colonisation, e.g. from direct contact with animals or via the food chain, could also play an important role in reducing the KpSC disease burden.
肺炎克雷伯菌复合种（KpSC）成员是机会性病原体，可引起严重且难治的感染。KpSC在非人类生态位中很常见，但这些菌群的临床相关性存在争议。
在本研究中，我们分析了2001年至2020年间在挪威收集的来自人类、动物和海洋来源的3255株全基因组测序分离株。我们在“同一个健康”背景下使用群体基因组学来评估不同来源内部和之间菌株、基因及其他临床相关遗传特征的多样性。我们进一步利用全基因组关联研究探索生态位富集特征，并调查了来自三个生态位的KpSC菌群之间溢出和连通性的证据。
我们发现不同生态位中的KpSC菌群各不相同但存在重叠。总体而言，不同来源之间以及来源内部均存在高度遗传多样性，附属基因组中近一半（49%）的基因与生态位重叠。此外，包括SL17、SL35、SL37、SL45、SL107和SL3010在内的几个亚系在不同来源中都很常见。除了编码气杆菌素的质粒和细菌素大肠杆菌素a与动物来源的KpSC相关外，几乎没有生态位富集特征。人类感染分离株之间的连通性最强，其次是来自人类携带、猪和双壳贝类的分离株。尽管这些来源在时间和地理上采样距离较远，但近5%的人类感染分离株在动物和海洋分离株中有近亲（≤22个替换）。近期存在有限但显著的溢出事件，包括编码毒力位点iuc3的质粒在猪和人之间的转移。
我们这项大型的“同一个健康”基因组研究强调，KpSC的人际传播比不同生态位之间的传播更为常见。不过，临床相关菌株和遗传特征在人类和非人类来源之间确实会发生溢出，不应被忽视。感染预防措施对于限制人类临床环境中的传播和减少感染至关重要。然而，预防导致定植的传播，例如通过直接接触动物或通过食物链传播，在减轻KpSC疾病负担方面也可能发挥重要作用。
