Table_3_Population genomic analysis of clinical ST15 Klebsiella pneumoniae strains in China.XLSX

ST15 Klebsiella pneumoniae (Kpn) is a growing public health concern in China and worldwide, yet its genomic and evolutionary dynamics in this region remain poorly understood. This study comprehensively elucidates the population genomics of ST15 Kpn in China by analyzing 287 publicly available genomes. The proportion of the genomes increased sharply from 2012 to 2021, and 92.3% of them were collected from the Yangtze River Delta (YRD) region of eastern China. Carbapenemase genes, including OXA-232, KPC-2, and NDM, were detected in 91.6% of the studied genomes, and 69.2% of which were multidrug resistant (MDR) and hypervirulent (hv). Phylogenetic analysis revealed four clades, C1 (KL112, 59.2%), C2 (mainly KL19, 30.7%), C3 (KL48, 0.7%) and C4 (KL24, 9.4%). C1 appeared in 2007 and was OXA-232-producing and hv; C2 and C4 appeared between 2005 and 2007, and both were KPC-2-producing but with different levels of virulence. Transmission clustering detected 86.1% (n = 247) of the enrolled strains were grouped into 55 clusters (2–159 strains) and C1 was more transmissible than others. Plasmid profiling revealed 88 plasmid clusters (PCs) that were highly heterogeneous both between and within clades. 60.2% (n = 53) of the PCs carrying AMR genes and 7 of which also harbored VFs. KPC-2, NDM and OXA-232 were distributed across 14, 4 and 1 PCs, respectively. The MDR-hv strains all carried one of two homologous PCs encoding iucABCD and rmpA2 genes. Pangenome analysis revealed two major coinciding accessory components predominantly located on plasmids. One component, associated with KPC-2, encompassed 15 additional AMR genes, while the other, linked to OXA-232, involved seven more AMR genes. This study provides essential insights into the genomic evolution of the high-risk ST15 CP-Kpn strains in China and warrants rigorous monitoring.

ST15型肺炎克雷伯菌（Klebsiella pneumoniae, Kpn）在中国乃至全球范围内日益成为公共卫生关注的焦点，但该菌株在我国的基因组学与演化动态仍有待深入解析。本研究通过分析287株公开可用的基因组序列，全面阐明了中国境内ST15型Kpn的群体基因组学特征。2012年至2021年间，该菌株的基因组占比急剧上升，其中92.3%的分离株采自中国东部的长江三角洲（Yangtze River Delta, YRD）地区。研究检测到，91.6%的受试基因组携带碳青霉烯酶基因，包括OXA-232、KPC-2及NDM；其中69.2%为多重耐药（multidrug resistant, MDR）且高毒力（hypervirulent, hv）菌株。系统发育分析显示其可分为4个进化簇：C1（KL112型，占比59.2%）、C2（主要为KL19型，占比30.7%）、C3（KL48型，占比0.7%）及C4（KL24型，占比9.4%）。C1于2007年出现，携带OXA-232且为高毒力菌株；C2与C4出现于2005至2007年间，均携带KPC-2，但毒力水平存在差异。传播聚类分析显示，86.1%（n=247）的入组菌株被划分为55个传播簇（单簇菌株数范围为2至159），且C1的传播能力强于其他进化簇。质粒分型分析共鉴定出88个质粒簇（plasmid clusters, PCs），各进化簇间及簇内的质粒簇均呈现高度异质性。其中60.2%（n=53）的质粒簇携带抗菌药物耐药（antimicrobial resistance, AMR）基因，另有7个质粒簇同时携带毒力因子（virulence factors, VFs）。KPC-2、NDM及OXA-232分别分布于14、4及1个质粒簇中。多重耐药且高毒力菌株均携带两种同源质粒簇之一，分别编码iucABCD与rmpA2基因。泛基因组分析揭示了两个主要的、共定位的附属基因组组分，且二者主要定位于质粒上。其中与KPC-2相关的组分额外包含15个抗菌药物耐药基因，而与OXA-232相关的组分则额外包含7个抗菌药物耐药基因。本研究为中国境内高风险ST15型产碳青霉烯酶肺炎克雷伯菌（CP-Kpn）的基因组演化提供了关键见解，同时提示需对该类菌株开展严格的监测工作。