blaKPC是肺炎克雷伯菌中流行最广的碳青霉烯酶基因，是困扰当前抗感染治疗最严重的耐药基因之一。产KPC酶肺炎克雷伯菌的大规模流行仅见于CC258型，IncFII质粒是最常见blaKPC播散质粒，但播撒机制不明。本项目组基于前期发现：携blaKPC的IncFII质粒含多种能被细菌适应性免疫系统CRISPR-Cas识别的Protospacer；该系统在CC258中缺失；CC258调控IncFII质粒与宿主接合的因子与非CC258显著不同，提出：CC258调控因子与IncFII质粒相互作用，是携blaKPC的CC258广泛播撒的主因；CRISPR-Cas限制IncFII-blaKPC质粒进入含此系统的宿主，促使其向无该系统的CC258传播，是辅因。本项目拟从CC258调控IncF质粒接合因子及CRISPR-Cas两方面入手，研究CC258广泛播散的机制，为建立有效的院感控制措施提供理论基础。

The blaKPC, the most prevalence carbapenemase gene in Klebsiella pneumoniae, become one of the most disturbing problems for clinical anti-infective therapy. K. pneumoniae clonal complex (CC) 258 is the most notorious lineage mediating the global dissemination of blaKPC, and IncFII account for majority of plasmids associated with blaKPC. However, the mechanism behind this phenomenon is still unclear. Based on the previous findings that all IncFII blaKPC-haboring (IncFII-blaKPC) plasmids possess protospacer corresponding to CRISPR-Cas system in K. pneumoniae while CRISPR-Cas system only exists in non-CC258 isolates, and that several host factors regulating plasmid conjugation in CC258 are apparently different with that in non-CC258, we proposed hypothesis that the interaction between host factors and IncFII plasmid is the key factor leading to the global dissemination of CC258 with blaKPC; additionally, CRISPR-Cas systems interfering the uptake and survival of IncFII-blaKPC plasmids within non-CC258 and promoting dissemination in CC258 also contribute in blaKPC spreading in CC258. We will concentrate on the interaction between host factors and IncFII plasmid and the function of CRISPR-Cas system to study the mechanism of CC258 dissemination, providing scientific evidence and data for establishment of effective control system to prevent hospital infection.