ABSTRACT

Hypervirulent Klebsiella pneumoniae (HvKP), which causes highly fatal infections, is a new threat to human health. In an attempt to investigate the underlying mechanisms of resistance to neutrophil-mediated killing and hence expression of high-level virulence by HvKP, we tested the binding affinity of HvKP strains to various types of human cells. Our data showed that HvKP exhibited weaker binding to both lung epithelial cells, intestinal Caco-2 cells and macrophages when compared to the classic, non-hypervirulent strains (cKP). Consistently, transconjugants that have acquired a rmpA or rmpA2-bearing plasmid were found to exhibit decreased adhesion to various types of human cells, and hence higher survival rate upon exposure to neutrophil cells. We further found that over production of hypermucoviscosity (HMV), but not capsular polysaccharide (CPS), contributed to the reduced binding and phagocytosis. The effect of hypermucoviscosity on enhancing HvKP virulence was further shown in human serum survival assays and animal experiments. Findings in this study therefore confirmed that rmpA/A2-mediated hypermucoviscosity in HvKP plays a key role in the pathogenesis of this organism through conferring the ability to evade neutrophil binding and phagocytosis.

摘要

高毒性肺炎克雷伯菌( HvKP ) 会导致高度致命的感染，是对人类健康的新威胁。为了研究抵抗嗜中性粒细胞介导的杀伤以及由此表达 HvKP 高水平毒力的潜在机制，我们测试了 HvKP 菌株对各种类型的人类细胞的结合亲和力。我们的数据显示，与经典的非高毒性菌株 (cKP) 相比，HvKP 与肺上皮细胞、肠 Caco-2 细胞和巨噬细胞的结合较弱。一致地，已获得rmpA或rmpA2发现携带质粒对各种类型的人类细胞的粘附性降低，因此在暴露于中性粒细胞时存活率更高。我们进一步发现，过度产生高粘液粘度 (HMV) 而不是荚膜多糖 (CPS)，导致结合和吞噬作用降低。在人血清存活测定和动物实验中进一步显示了高粘液粘度对增强 HvKP 毒力的影响。因此，本研究中的结果证实，rmpA/A2介导的 HvKP 中的高黏液粘度通过赋予逃避中性粒细胞结合和吞噬作用的能力，在该生物体的发病机制中起关键作用。