整合接合元件ICE258.2在产KPC酶肺炎克雷伯菌大规模流行中的作用和机制研究

肺炎克雷伯菌（Kp）可引起血流感染和肺炎等严重感染，特别是碳青霉烯耐药肺炎克雷伯菌（CRKp）已在全球范围迅速蔓延，对人类健康造成了严重威胁。目前靠简单的耐药表型、克隆传播或质粒转移模型已无法解释CRKp在全球范围的大流行。课题组前期工作显示Kp整合接合元件ICE258.2敲除株生长速度比野生株慢约20%，且质粒转移频率和稳定性比野生株显著降低，提示ICE258.2可能在耐药质粒与宿主菌作用中发挥重要功能。课题组拟通过研究不同碳青霉烯耐药质粒在不同遗传背景下对Kp宿主的适应性，分析耐药质粒与宿主菌的相互作用；构建ICE258.2敲除株探索其对质粒接合、稳定性和适应性代价的作用；通过WGS和RNAseq研究适应性代价下宿主菌突变及表达谱变化，系统性探索ICE258.2在耐药质粒和宿主菌相互适应中的作用。本研究将有助于破解产KPC酶Kp大规模流行的分子机制，推动其引起的感染性疾病的预防和治疗。

Klebsiella pneumoniae (KP) can cause serious infection such as blood stream infections and pneumonia, especially carbapenem resistant Klebsiella pneumoniae (CRKP) has spread rapidly all over the world, which poses a serious threat to human health. Currently, models of simple clonal spread or plasmid transfer fails to explain tne molecular epidemiology of the CRKP epdemic. The previous work of our group showed that the knockout strain of ICE258.2 grew about 20% slower than the wild strain, and the plasmid transfer frequency and stability were significantly lower than the wild strain, suggesting that ICE258.2 may play an important role in the plasmid-host adaptation. We plan to study the adaptability of different carbapenem resistant plasmids to KP host under different genetic background, analyze the interaction between resistant plasmids and host bacteria; construct ICE258.2 knockout strain to explore its role in plasmid conjugation, stability and fitness cost; study the mutation and expression changes of host bacteria under adaptability cost through WGS and RNAseq to explore the role of ICE258.2 systematically. This study will help to understand the molecular mechanism of KPC producing KP and promote the prevention and treatment of infectious diseases caused by CRKP.