Genomic features of resistant Klebsiella pneumonia, isolated from the bloodstream and cerebrospinal fluid of pediatric hospital patients

O. Voronina, Марина S. Kunda, N. Ryzhova, E. Aksenova, Z. Sadeeva, I. Novikova, Anna V. Lazareva, O. Karaseva, А. P. Fisenko, A. L. Gintsburg
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Abstract

Introduction. Carbapenemase-producing Klebsiella pneumoniae (CP-Kp), which are international high-risk clones, have become a problem of utmost importance. CP-Kps, adapting to the hospital environment, evolve into convergent pathotypes. Such variants combine traits of two genetic lineages: multidrug resistant (MDR) and hypervirulent. The pathotypes, along with MDR K. pneumoniae, pose an exceptional threat to young patients during systemic infection. The objective of this study is the detailed molecular genetic analysis of MDR isolates of K. pneumoniae detected during the monitoring of resistant Gram-negative bacteria at the National Medical Research Center for Children’s Health in 2014–2021. Materials and methods. Whole-genome sequencing with a subsequent bioinformatics analysis of eight MDR isolates from the bloodstream and cerebrospinal fluid. Results. MDR isolates belonged to 4 sublineages (SL): SL307, SL395, SL29 and SL1198. In the genomes of 6 pangrug-resistant (PDR) isolates, genes associated with resistance to all categories of antibiotics recommended for Enterobacteriaceae therapy were identified. Plasmids were present in all genomes. In 6 isolates, plasmids contained heavy metal ion resistance operons in addition to antibiotic resistance genes. Prophages within the plasmids were also involved in the transfer of resistance genes. The ST395 isolate from the cerebrospinal fluid belonged to the convergent pathotype in terms of resistance and virulence. Comparison of genomes within SLs revealed recombination events in the K- and O-locus regions and the Yersiniabactin operon. Conclusion. Thus, in a sample of resistant K. pneumoniae isolated from bloodstream and cerebrospinal fluid, 6 PDR isolates were detected, one of which belongs to the convergent pathotype ST395.
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从儿科医院病人血液和脑脊液中分离出的耐药肺炎克雷伯菌的基因组特征
导言。产碳青霉烯酶肺炎克雷伯氏菌(CP-Kp)是国际高危克隆,已成为一个极其重要的问题。产碳青霉烯酶肺炎克雷伯氏菌(CP-Kp)是一种国际高风险克隆,已成为一个极其重要的问题。这些变种结合了两个基因系的特征:耐多药(MDR)和高病毒性。这些病原体与耐多药肺炎 K.菌一起,在全身感染时对年轻患者构成特殊威胁。本研究的目的是对 2014-2021 年国家儿童健康医学研究中心监测耐药革兰氏阴性菌期间检测到的肺炎克雷伯菌 MDR 分离物进行详细的分子遗传学分析。材料与方法。对来自血液和脑脊液的 8 株 MDR 分离物进行全基因组测序和随后的生物信息学分析。结果。MDR 分离物属于 4 个亚系(SL):SL307、SL395、SL29 和 SL1198。在 6 个耐潘古(PDR)分离株的基因组中,发现了与对推荐用于肠杆菌科治疗的各类抗生素的耐药性相关的基因。所有基因组中都存在质粒。在 6 个分离株中,质粒除了抗生素耐药基因外,还含有重金属离子耐药操作子。质粒中的噬菌体也参与了抗性基因的转移。从脑脊液中分离出的 ST395 在抗药性和毒力方面属于趋同病原型。对SL内的基因组进行比较后发现,在K-和O-病灶区以及Yersiniabactin操作子中存在重组事件。结论因此,在从血流和脑脊液中分离出的耐药肺炎克菌样本中,发现了 6 个 PDR 分离物,其中一个属于趋同病原型 ST395。
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