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Abstract：
BACKGROUND: Certain clonal complexes (CCs) of Klebsiella pneumoniae such as CC147 (ST147 and ST392) are major drivers of blaNDM dissemination across the world. ST147 has repeatedly reported from our geographical region, but its population dynamics and evolutionary trajectories need to be further studied.
METHODS: Comparative genomic analysis of 51 carbapenem-nonsusceptible strains as well as three hypervirulent K. pneumoniae (hvKp) recovered during 16-months of surveillance was performed using various bioinformatics tools. We investigated the genetic proximity of our ST147 strains with publicly available corresponding genomes deposited globally and from neighbor countries in our geographic region.
RESULTS: While IncL/M plasmid harboring blaOXA-48 was distributed among divergent clones, blaNDM-1 was circulated by twenty of the 25 CC147 dominant clone and were mostly recovered from the ICU. The NDM-1 core structure was bracketed by a single isoform of mobile genetic elements (MGEs) [ΔISKpn26-NDM-TnAs3-ΔIS3000-Tn5403] and was located on Col440I plasmid in 68.7% of ST392. However, various arrangements of MGEs including MITESen1/MITESen1 composite transposon or combination of MITESen1/ISSen4/IS903B/IS5/ISEhe3 on IncFIb (pB171) were identified in ST147. It seems that ST392 circulated blaNDM-1 in 2018 before being gradually replaced by ST147 from the middle to the end of sample collection in 2019. ST147 strains possessed the highest number of resistance markers and showed high genetic similarity with four public genomes that harbored blaNDM-1 on the same replicon type. Mainly, there was a convergence between clusters and isolated neighboring countries in the minimum-spanning tree. A conserved arrangement of resistance markers/MGEs was linked to methyltransferase armA which was embedded in class 1 integron in 8 isolates of ST147/ST48 high-risk clones.
CONCLUSIONS: Our findings highlight the dynamic nature of blaNDM-1 transmission among K. pneumoniae in Iran that occurs both clonally and horizontally via various combinations of MGEs. This is the first analysis of Iranian ST147/NDM + clone in the global context.
METHODS: Comparative genomic analysis of 51 carbapenem-nonsusceptible strains as well as three hypervirulent K. pneumoniae (hvKp) recovered during 16-months of surveillance was performed using various bioinformatics tools. We investigated the genetic proximity of our ST147 strains with publicly available corresponding genomes deposited globally and from neighbor countries in our geographic region.
RESULTS: While IncL/M plasmid harboring blaOXA-48 was distributed among divergent clones, blaNDM-1 was circulated by twenty of the 25 CC147 dominant clone and were mostly recovered from the ICU. The NDM-1 core structure was bracketed by a single isoform of mobile genetic elements (MGEs) [ΔISKpn26-NDM-TnAs3-ΔIS3000-Tn5403] and was located on Col440I plasmid in 68.7% of ST392. However, various arrangements of MGEs including MITESen1/MITESen1 composite transposon or combination of MITESen1/ISSen4/IS903B/IS5/ISEhe3 on IncFIb (pB171) were identified in ST147. It seems that ST392 circulated blaNDM-1 in 2018 before being gradually replaced by ST147 from the middle to the end of sample collection in 2019. ST147 strains possessed the highest number of resistance markers and showed high genetic similarity with four public genomes that harbored blaNDM-1 on the same replicon type. Mainly, there was a convergence between clusters and isolated neighboring countries in the minimum-spanning tree. A conserved arrangement of resistance markers/MGEs was linked to methyltransferase armA which was embedded in class 1 integron in 8 isolates of ST147/ST48 high-risk clones.
CONCLUSIONS: Our findings highlight the dynamic nature of blaNDM-1 transmission among K. pneumoniae in Iran that occurs both clonally and horizontally via various combinations of MGEs. This is the first analysis of Iranian ST147/NDM + clone in the global context.
摘要：
背景：肺炎克雷伯菌的某些克隆复合物（CC），例如CC147（ST147和ST392）是全球blaNDM传播的主要驱动因素。ST147多次从我们的地理区域报告，但是它的种群动态和进化轨迹需要进一步研究。
方法：使用各种生物信息学工具对在16个月监测期间回收的51株碳青霉烯类非敏感菌株以及3株高毒力肺炎克雷伯菌（hvKp）进行比较基因组分析。我们调查了我们的ST147菌株与全球和我们地理区域邻国公开提供的相应基因组的遗传邻近性。
结果：虽然携带blaOXA-48的IncL/M质粒分布在不同的克隆中，blaNDM-1由25个CC147显性克隆中的20个传播，大部分从ICU中回收。NDM-1核心结构由可移动遗传元件（MGEs）的单个同工型[ΔISKpn26-NDM-TnAs3-ΔIS3000-Tn5403]包围，并位于ST392的68.7％的Col440I质粒上。然而,在ST147中鉴定了MGE的各种排列,包括MITESen1/MITESen1复合转座子或MITESen1/ISSen4/IS903B/IS5/ISEhe3在IncFIb(pB171)上的组合。似乎ST392在2018年传播blaNDM-1，然后在2019年从样本采集的中间到最后逐渐被ST147取代。ST147菌株具有最高数量的抗性标记，并且与四个在相同复制子类型上带有blaNDM-1的公共基因组表现出高度的遗传相似性。主要是,在最小生成树中，集群和孤立的邻国之间存在趋同。抗性标记/MGE的保守排列与甲基转移酶armA连接，该甲基转移酶armA嵌入ST147/ST48高风险克隆的8个分离株的1类整合子中。
结论：我们的发现强调了伊朗肺炎克雷伯菌之间blaNDM-1传播的动态性质，该传播通过各种MGE组合发生克隆和水平。这是在全球范围内对伊朗ST147/NDM克隆的首次分析。
方法：使用各种生物信息学工具对在16个月监测期间回收的51株碳青霉烯类非敏感菌株以及3株高毒力肺炎克雷伯菌（hvKp）进行比较基因组分析。我们调查了我们的ST147菌株与全球和我们地理区域邻国公开提供的相应基因组的遗传邻近性。
结果：虽然携带blaOXA-48的IncL/M质粒分布在不同的克隆中，blaNDM-1由25个CC147显性克隆中的20个传播，大部分从ICU中回收。NDM-1核心结构由可移动遗传元件（MGEs）的单个同工型[ΔISKpn26-NDM-TnAs3-ΔIS3000-Tn5403]包围，并位于ST392的68.7％的Col440I质粒上。然而,在ST147中鉴定了MGE的各种排列,包括MITESen1/MITESen1复合转座子或MITESen1/ISSen4/IS903B/IS5/ISEhe3在IncFIb(pB171)上的组合。似乎ST392在2018年传播blaNDM-1，然后在2019年从样本采集的中间到最后逐渐被ST147取代。ST147菌株具有最高数量的抗性标记，并且与四个在相同复制子类型上带有blaNDM-1的公共基因组表现出高度的遗传相似性。主要是,在最小生成树中，集群和孤立的邻国之间存在趋同。抗性标记/MGE的保守排列与甲基转移酶armA连接，该甲基转移酶armA嵌入ST147/ST48高风险克隆的8个分离株的1类整合子中。
结论：我们的发现强调了伊朗肺炎克雷伯菌之间blaNDM-1传播的动态性质，该传播通过各种MGE组合发生克隆和水平。这是在全球范围内对伊朗ST147/NDM克隆的首次分析。
