An Assessment of Siderophore Production, Mucoviscosity, and Mouse Infection Models for Defining the Virulence Spectrum of Hypervirulent Klebsiella pneumoniae.
An Assessment of Siderophore Production, Mucoviscosity, and Mouse Infection Models for Defining the Virulence Spectrum of Hypervirulent Klebsiella pneumoniae.
复制标题
用于定义高毒力肺炎克雷伯菌毒力谱的铁载体产生、粘液粘度和小鼠感染模型的评估。
DOI：
10.1128/msphere.00045-21
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发表时间：
2021-03-24
期刊：
影响因子：
4.8
通讯作者：
McGann P
中科院分区：
文献类型：
--
作者：
Russo TA;MacDonald U;Hassan S;Camanzo E;LeBreton F;Corey B;McGann P
高毒力肺炎克雷伯菌（hvKp）细菌比经典肺炎克雷伯菌（cKp）更毒，因此在临床表现和管理上存在差异。目前尚不清楚是否所有hvKp分离株都具有相似的致病潜力。本报告评估了铁载体产生、黏性和小鼠感染对确定hvKp毒力谱的效用。基于CD1小鼠皮下（SQ）攻毒模型，鉴定并定义了三个菌株队列：(i)全毒力hvKp菌株（fvhvKp），攻毒接种量(CI)≤103 CFU时致死；（ii）部分毒力强的hvKp菌株（pvhvKp）， CI为103 ~ 107 CFU时致死；（iii）典型肺炎克雷伯菌，CI为107 CFU时不致死。定量铁载体和黏性试验将fvhvKp和pvhvKp菌株与cKp菌株区分开来，但无法区分fvhvKp和pvhvKp菌株队列。然而，CD1小鼠的SQ攻击和CD1和BALB/c小鼠的腹腔（IP）攻击，而不是C57BL/6小鼠，能够区分fvhvKp和pvhvKp菌株；CD1小鼠的SQ攻击可能具有最大的敏感性。CD1小鼠的SQ攻击和三种小鼠品系的IP攻击均能分化出cKp和hvKp。这些数据确定了确定hvKP毒株相对毒力的方法。目前尚不清楚小鼠中观察到的hvKp毒力差异是否转化为人类感染。然而，这些数据可用于将随机收集的肺炎克雷伯菌菌株分类为fvhvKp和pvhvKp菌株队列，并评估临床表现和结局的差异。hvKp菌株的致病潜力主要是由一个大毒力质粒介导的。充分表达高毒表型所需的最小基因集尚未确定。一些报道描述了hvKp菌株只具有部分毒力质粒；临床结果尚不清楚。因此，本报告的目的是确定hvKp菌株之间的毒力是否存在差异，如果存在差异，如何最好地确定hvKp分离株的相对毒力。数据显示hvKp在CD1和BALB/c小鼠感染模型中的致病潜力不同。相比之下，铁载体产量和粘液粘度的测量无法区分小鼠中观察到的hvKp分离株毒力的差异。这一信息可用于未来的研究，以确定完全致病性hvKp和部分致病性hvKp之间差异的机制，以及在小鼠中观察到的差异是否转化为人类疾病。
Hypervirulent Klebsiella pneumoniae (hvKp) bacteria are more virulent than classical K. pneumoniae (cKp) with resultant differences in clinical manifestations and management. It is unclear whether all hvKp isolates share a similar pathogenic potential. This report assessed the utility of siderophore production, mucoviscosity, and murine infection for defining the virulence spectrum of hvKp. Three strain cohorts were identified and defined based on the CD1 mouse subcutaneous (SQ) challenge model: (i) fully virulent hvKp strains (fvhvKp), lethal at a challenge inoculum (CI) of ≤103 CFU; (ii) partially virulent hvKp strains (pvhvKp), lethal at a CI of >103 to 107 CFU; (iii) classical K. pneumoniae, not lethal at a CI of 107 CFU. Quantitative siderophore and mucoviscosity assays differentiated fvhvKp and pvhvKp strains from cKp strains but were unable to differentiate between the fvhvKP and pvhvKP strain cohorts. However, SQ challenge of CD1 mice and intraperitoneal (IP) challenge of CD1 and BALB/c mice, but not C57BL/6 mice, were able to discriminate between an fvhvKp and a pvhvKp strain; SQ challenge of CD1 mice may have the greatest sensitivity. cKp was differentiated from hvKp both by SQ challenge of CD1 mice and IP challenge of all three mouse strains. These data identify a means to define the relative virulence of hvKP strains. It remains unclear whether the observed differences of hvKp virulence in mice translates to human infection. However, these data can be used to sort random collections of K. pneumoniae strains into fvhvKp and pvhvKp strain cohorts and assess for differences in clinical manifestations and outcomes. IMPORTANCE The pathogenic potential of hvKp strains is primarily mediated by a large virulence plasmid. The minimal set of genes required for the full expression of the hypervirulent phenotype is undefined. A number of reports describe hvKp strains possessing only a portion of the virulence plasmid; the clinical consequences of this are unclear. Therefore, the goal of this report was to determine whether virulence among hvKp strains varied and, if so, how to best identify the relative virulence of hvKp isolates. Data demonstrate hvKp pathogenic potential varies in CD1 and BALB/c murine infection models. In contrast, measurements of siderophore production and mucoviscosity were unable to discriminate the differences in hvKp isolate virulence observed in mice. This information can be used in future studies to determine the mechanisms responsible for differences between fully virulent hvKp and partially virulent hvKp and whether the differences observed in mice translate to disease in humans.