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Identifying virulence determinants of multidrug-resistant Klebsiella pneumoniae in Galleria mellonella
Pathogens and Disease ( IF 2.7 ) Pub Date : 2021-01-27 , DOI: 10.1093/femspd/ftab009
Sebastian Bruchmann 1, 2 , Theresa Feltwell 2, 3 , Julian Parkhill 1 , Francesca L Short 2, 3, 4
Affiliation  

Infections caused by Klebsiella pneumoniae are a major public health threat. Extensively drug-resistant and even pan-resistant strains have been reported. Understanding K. pneumoniae pathogenesis is hampered by the fact that murine models of infection offer limited resolution for non-hypervirulent strains which cause the majority of infections. The insect Galleria mellonella larva is a widely used alternative model organism for bacterial pathogens. We have performed genome-scale fitness profiling of a multidrug-resistant K. pneumoniae ST258 strain during infection of G. mellonella, to determine if this model is suitable for large-scale virulence factor discovery in this pathogen. Our results demonstrated a dominant role for surface polysaccharides in infection, with contributions from siderophores, cell envelope proteins, purine biosynthesis genes and additional genes of unknown function. Comparison with a hypervirulent strain, ATCC 43816, revealed substantial overlap in important infection-related genes, as well as additional putative virulence factors specific to ST258, reflecting strain-dependent fitness effects. Our analysis also identified a role for the metalloregulatory protein NfeR (YqjI) in virulence. Overall, this study offers new insight into the infection fitness landscape of K. pneumoniae, and provides a framework for using the highly flexible and easily scalable G. mellonella infection model to dissect molecular virulence mechanisms of bacterial pathogens.

中文翻译:

鉴定大肠菌群中耐多药肺炎克雷伯菌的毒力决定因素

由肺炎克雷伯菌引起的感染是主要的公共卫生威胁。已经报道了广泛耐药甚至泛耐药菌株。了解肺炎克雷伯菌的发病机制受到以下事实的阻碍:小鼠感染模型对导致大多数感染的非高毒力菌株提供有限的分辨率。昆虫 Galleria mellonella 幼虫是细菌病原体的一种广泛使用的替代模式生物。我们在 G. mellonella 感染期间对耐多药肺炎克雷伯菌 ST258 菌株进行了基因组规模的适应性分析,以确定该模型是否适用于该病原体的大规模毒力因子发现。我们的结果证明了表面多糖在感染中的主要作用,其中铁载体、细胞包膜蛋白、嘌呤生物合成基因和功能未知的其他基因。与高毒力菌株 ATCC 43816 的比较显示,重要的感染相关基因存在大量重叠,以及 ST258 特有的额外假定毒力因子,反映了菌株依赖性适应度效应。我们的分析还确定了金属调节蛋白 NfeR (YqjI) 在毒力中的作用。总体而言,这项研究为肺炎克雷伯菌的感染适应性提供了新的见解,并为使用高度灵活且易于扩展的 G. mellonella 感染模型来剖析细菌病原体的分子毒力机制提供了一个框架。以及特定于 ST258 的其他推定毒力因子,反映了应变依赖性适应度效应。我们的分析还确定了金属调节蛋白 NfeR (YqjI) 在毒力中的作用。总体而言,这项研究为肺炎克雷伯菌的感染适应性提供了新的见解,并为使用高度灵活且易于扩展的 G. mellonella 感染模型来剖析细菌病原体的分子毒力机制提供了一个框架。以及特定于 ST258 的其他推定毒力因子,反映了应变依赖性适应度效应。我们的分析还确定了金属调节蛋白 NfeR (YqjI) 在毒力中的作用。总体而言,这项研究为肺炎克雷伯菌的感染适应性提供了新的见解,并为使用高度灵活且易于扩展的 G. mellonella 感染模型来剖析细菌病原体的分子毒力机制提供了一个框架。
更新日期:2021-01-27
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