Department of Microbiology, All India Institute of Medical Sciencesgrid.413618.9, New Delhi, India.
ICMR AIIMS Computational Genomics Centre, Division of Biomedical Informatics, Indian Council of Medical Researchgrid.19096.37, New Delhi, India.
Microbiol Spectr. 2022 Oct 26;10(5):e0037622. doi: 10.1128/spectrum.00376-22. Epub 2022 Aug 31.
Hypervirulent Klebsiella pneumoniae (hvKp) is a hypermucoviscous phenotype of classical Klebsiella pneumoniae (cKp) that causes serious infections in the community. The recent emergence of multidrug-resistant hvKp isolates (producing extended-spectrum beta-lactamases and carbapenemases) along with other virulence factors in health care settings has become a clinical crisis. Here, we aimed to compare the distribution of virulence determinants and antimicrobial resistance (AMR) genes in relation to various sequence types (STs) among the clinical hvKp isolates from both settings, to reinforce our understanding of their epidemiology and pathogenic potential. A total of 120 K. pneumoniae isolates confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry were selected. hvKp was phenotypically identified by string test and genotypically confirmed by the presence of the gene using PCR. Molecular characterization of hvKp isolates was done by whole-genome sequencing (WGS). Of the K. pneumoniae isolates, 11.6% (14/120) isolates were confirmed as hvKp by PCR (9.1% [11/120] string positive and 3.3% [4/120] positive by both methods); these were predominantly isolated from bloodstream infection (50%, 7/14), urinary tract infection (29%, 4/14), and respiratory tract infection (21%, 3/14). For all 14 hvKp infections, for 14.2% the source was in the community and for 85.7% the source was a health care setting. Two virulent plasmids were identified by WGS among the hvKp isolates from both settings. K64 was found to be the commonest capsular serotype (28.5%, 4/14), and ST2096 was the most common ST (28.5%, 4/14) by WGS. Two new STs were revealed: ST231 (reported to cause outbreaks) and ST43. The genome of one isolate was determined to be carrying AMR genes (, , , , , etc.) in addition to virulence genes, highlighting the clonal spread of hvKp in both community and health care settings. To date, studies comparing the genomic characteristics of hospital- and community-acquired hvKp were very few in India. In this study, we analyzed the clinical and genomic characteristics of hvKp isolates from hospital and community settings. ST2096 was found as the most common ST along with novel STs ST231 and ST43. Our study also revealed the genome is simultaneously carrying AMR as well as virulence genes in isolates from both settings, highlighting the emergence of MDR hvKp STs integrated with virulence genes in both community and health care settings. Thus, hvKp may present a serious global threat, and essential steps are needed to prevent its further dissemination.
高毒力肺炎克雷伯菌（hvKp）是经典肺炎克雷伯菌（cKp）的一种高黏液表型，可导致社区中严重的感染。最近，在医疗机构中出现了多药耐药 hvKp 分离株（产生扩展谱β-内酰胺酶和碳青霉烯酶）以及其他毒力因子，这已成为临床危机。在这里，我们旨在比较与各种序列类型（ST）相关的临床 hvKp 分离株的毒力决定因素和抗微生物药物耐药（AMR）基因的分布，以加强我们对其流行病学和发病机制的理解。共选择了 120 株经基质辅助激光解吸电离飞行时间质谱法确认的肺炎克雷伯菌。通过字符串试验对 hvKp 进行表型鉴定，通过 PCR 检测 基因的存在对 hvKp 进行基因确认。使用全基因组测序（WGS）对 hvKp 分离株进行分子特征分析。在肺炎克雷伯菌分离株中，11.6%（14/120）的分离株通过 PCR 确认为 hvKp（9.1%[11/120]字符串阳性，3.3%[4/120]两种方法均阳性）；这些分离株主要从血流感染（50%，7/14）、尿路感染（29%，4/14）和呼吸道感染（21%，3/14）中分离出来。对于所有 14 例 hvKp 感染，14.2%的来源是社区，85.7%的来源是医疗机构。通过对来自两个环境的 hvKp 分离株进行 WGS 分析，发现了两种毒力质粒。通过 WGS 发现 K64 是最常见的荚膜血清型（28.5%，4/14），ST2096 是最常见的 ST（28.5%，4/14）。揭示了两个新的 ST：ST231（据报道可引起暴发）和 ST43。一个分离株的基因组被确定携带 AMR 基因（、、、、、等）除了毒力基因外，这突出了 hvKp 在社区和医疗机构中的克隆传播。到目前为止，比较医院和社区获得性 hvKp 基因组特征的研究在印度非常少。在这项研究中，我们分析了来自医院和社区环境的 hvKp 分离株的临床和基因组特征。发现 ST2096 是最常见的 ST，同时还发现了新型 STs ST231 和 ST43。我们的研究还揭示了分离株的基因组同时携带 AMR 和毒力基因，这表明 MDR hvKp ST 与社区和医疗机构中的毒力基因整合在一起。因此，hvKp 可能是一种严重的全球威胁，需要采取必要措施防止其进一步传播。
