肺炎克雷伯菌中rmp基因座变体的基因组和功能分析

Genomic and functional analysis of rmp locus variants in Klebsiella pneumoniae.

作者信息

Lam Margaret M C, Salisbury Stephen M, Treat Logan P, Wick Ryan R, Judd Louise M, Wyres Kelly L, Brisse Sylvain, Walker Kimberly A, Miller Virginia L, Holt Kathryn E

机构信息

Department of Infectious Diseases, School of Translational Medicine, Monash University, The Burnet Institute, Level 285 Commercial Rd, Melbourne, 3004, Australia.

Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

出版信息

Genome Med. 2025 Apr 9;17(1):36. doi: 10.1186/s13073-025-01461-5.

DOI:10.1186/s13073-025-01461-5

PMID:40205597

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11984045/

Abstract

BACKGROUND

Klebsiella pneumoniae is an opportunistic pathogen and a leading cause of healthcare-associated infections in hospitals, which are frequently antimicrobial resistant (AMR). Exacerbating the public health threat posed by K. pneumoniae, some strains also harbour additional hypervirulence determinants typically acquired via mobile genetic elements such as the well-characterised large virulence plasmid KpVP-1. The rmpADC locus is considered a key virulence feature of K. pneumoniae and is associated with upregulated capsule expression and the hypermucoid phenotype, which can enhance virulence by contributing to serum resistance. Typically such strains have been susceptible to all antimicrobials besides ampicillin; however, the recent emergence of AMR hypermucoid strains is concerning.

METHODS

Here, we investigate the genetic diversity, evolution, mobilisation and prevalence of rmpADC, in a dataset of 14,000 genomes from isolates of the Klebsiella pneumoniae species complex, and describe the RmST virulence typing scheme for tracking rmpADC variants for the purposes of genomic surveillance. Additionally, we examine the functionality of representatives for variants of rmpADC introduced into a mutant strain lacking its native rmpADC locus.

RESULTS

The rmpADC locus was detected in 7% of the dataset, mostly from genomes of K. pneumoniae and a very small number of K. variicola and K. quasipneumoniae. Sequence variants of rmpADC grouped into five distinct lineages (rmp1, rmp2, rmp2A, rmp3 and rmp4) that corresponded to unique mobile elements, and were differentially distributed across different populations (i.e. clonal groups) of K. pneumoniae. All variants were demonstrated to produce enhanced capsule production and hypermucoviscosity.

CONCLUSIONS

These results provide an overview of the diversity and evolution of a prominent K. pneumoniae virulence factor and support the idea that screening for rmpADC in K. pneumoniae isolates and genomes is valuable to monitor the emergence and spread of hypermucoid K. pneumoniae, including AMR strains.

摘要

背景

肺炎克雷伯菌是一种机会致病菌，是医院医疗相关感染的主要病因，这些感染通常具有抗菌耐药性（AMR）。一些菌株还携带其他通常通过移动遗传元件获得的高毒力决定因素，例如特征明确的大毒力质粒KpVP - 1，这加剧了肺炎克雷伯菌对公共卫生的威胁。rmpADC基因座被认为是肺炎克雷伯菌的关键毒力特征，与上调的荚膜表达和高黏液样表型相关，这可通过促进血清抗性来增强毒力。通常，除氨苄西林外，此类菌株对所有抗菌药物敏感；然而，最近出现的AMR高黏液样菌株令人担忧。

方法

在此，我们在来自肺炎克雷伯菌物种复合体分离株的14000个基因组数据集中，研究rmpADC的遗传多样性、进化、移动性和流行情况，并描述用于基因组监测追踪rmpADC变体的RmST毒力分型方案。此外，我们研究了引入缺乏其天然rmpADC基因座的突变菌株中的rmpADC变体代表的功能。

结果

在7%的数据集中检测到rmpADC基因座，主要来自肺炎克雷伯菌的基因组，以及极少数的Variicola克雷伯菌和准肺炎克雷伯菌的基因组。rmpADC的序列变体分为五个不同的谱系（rmp1、rmp2、rmp2A、rmp3和rmp4），它们对应于独特的移动元件，并在肺炎克雷伯菌的不同群体（即克隆群）中差异分布。所有变体均显示出增强的荚膜产生和高黏液性。