Teng Gaoqin, Qin Qiuying, Ding Shuo, Wu Yanchao, Fu Yingying, Zhang Meng, Yang Xiaoqiang, Jin Ye, Xu Zhijiang, Huang Man
Department of General Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education, Zhejiang, China.
Front Microbiol. 2025 May 15;16:1577629. doi: 10.3389/fmicb.2025.1577629. eCollection 2025.
Hypervirulent (hvKp) is a major pathogen causing community-acquired infections, particularly severe diseases such as liver abscesses. Although extensive research has been conducted on the virulence mechanisms of hvKp and the genetic properties of resistance plasmids, studies on the adaptive evolution of clinical strains within the host are still limited. This study aimed to investigate the impact of genetic mutations on phenotypic changes in high-virulence within a host environment. We isolated three strains of from the same patient, two of which had identical genetic backgrounds but exhibited distinct phenotypic traits. Comparative genomic analysis was performed to identify genetic differences. A nucleotide mutation in the wzc gene was identified as a potential factor associated with changes in the mucoid phenotype. This mutation was verified using string tests and anti-centrifugal assays. Additionally, bioassays and animal infection models were conducted to further validate the findings. The comparative genomic analysis revealed a nucleotide mutation in the wzc gene, which was associated with changes in the mucoid phenotype of the strain. This was confirmed through string tests and anti-centrifugal assays. experiments and animal infection models suggested that hvKp adapts to the host by reducing capsular polysaccharide synthesis, thereby trading off some virulence for enhanced colonization capabilities. Our findings indicate that genetic mutations in hvKp can lead to significant phenotypic changes that facilitate adaptation within the host. The observed reduction in capsular polysaccharide synthesis appears to be a trade-off between virulence and colonization ability. This study provides insights into the adaptive evolution of hvKp and highlights the importance of considering intrahost genetic changes when studying the pathogenesis of hvKp. Future research should focus on further elucidating the mechanisms underlying these adaptations and their clinical implications.
高毒力肺炎克雷伯菌（hvKp）是引起社区获得性感染的主要病原体，尤其是导致肝脓肿等严重疾病。尽管已经对hvKp的毒力机制和耐药质粒的遗传特性进行了广泛研究，但关于临床菌株在宿主体内的适应性进化的研究仍然有限。本研究旨在调查基因突变对宿主环境中高毒力菌株表型变化的影响。我们从同一患者体内分离出三株菌株，其中两株具有相同的遗传背景，但表现出不同的表型特征。进行了比较基因组分析以确定遗传差异。wzc基因中的一个核苷酸突变被确定为与黏液样表型变化相关的潜在因素。使用拉丝试验和抗离心试验对该突变进行了验证。此外，还进行了生物测定和动物感染模型以进一步验证研究结果。比较基因组分析揭示了wzc基因中的一个核苷酸突变，该突变与菌株的黏液样表型变化有关。这通过拉丝试验和抗离心试验得到了证实。实验和动物感染模型表明，hvKp通过减少荚膜多糖合成来适应宿主，从而以牺牲一些毒力为代价增强定植能力。我们的研究结果表明，hvKp中的基因突变可导致显著的表型变化，从而促进在宿主体内的适应。观察到的荚膜多糖合成减少似乎是毒力和定植能力之间的权衡。本研究为hvKp的适应性进化提供了见解，并强调了在研究hvKp的发病机制时考虑宿主内基因变化的重要性。未来的研究应集中在进一步阐明这些适应的潜在机制及其临床意义上。
