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Visualizing Staphylococcus aureus pathogenic membrane modification within the host infection environment by multimodal imaging mass spectrometry
Cell Chemical Biology ( IF 8.6 ) Pub Date : 2022-06-01 , DOI: 10.1016/j.chembiol.2022.05.004
William J Perry 1 , Caroline M Grunenwald 2 , Raf Van de Plas 3 , James C Witten 4 , Daniel R Martin 5 , Suneel S Apte 5 , James E Cassat 6 , Gösta B Pettersson 4 , Richard M Caprioli 7 , Eric P Skaar 2 , Jeffrey M Spraggins 8
Affiliation  

Bacterial pathogens have evolved virulence factors to colonize, replicate, and disseminate within the vertebrate host. Although there is an expanding body of literature describing how bacterial pathogens regulate their virulence repertoire in response to environmental signals, it is challenging to directly visualize virulence response within the host tissue microenvironment. Multimodal imaging approaches enable visualization of host-pathogen molecular interactions. Here we demonstrate multimodal integration of high spatial resolution imaging mass spectrometry and microscopy to visualize Staphylococcus aureus envelope modifications within infected murine and human tissues. Data-driven image fusion of fluorescent bacterial reporters and matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance imaging mass spectrometry uncovered S. aureus lysyl-phosphatidylglycerol lipids, localizing to select bacterial communities within infected tissue. Absence of lysyl-phosphatidylglycerols is associated with decreased pathogenicity during vertebrate colonization as these lipids provide protection against the innate immune system. The presence of distinct staphylococcal lysyl-phosphatidylglycerol distributions within murine and human infections suggests a heterogeneous, spatially oriented microbial response to host defenses.



中文翻译:

通过多模态成像质谱可视化宿主感染环境中金黄色葡萄球菌致病膜的修饰

细菌病原体已进化出毒力因子,可在脊椎动物宿主内定植、复制和传播。尽管有越来越多的文献描述细菌病原体如何响应环境信号调节其毒力库,但直接可视化宿主组织微环境内的毒力反应具有挑战性。多模态成像方法可以实现宿主-病原体分子相互作用的可视化。在这里,我们展示了高空间分辨率成像质谱和显微镜的多模式集成,以可视化受感染的小鼠和人体组织内的金黄色葡萄球菌包膜修饰。荧光细菌报告基因和基质辅助激光解吸/电离傅里叶变换离子回旋共振成像质谱法的数据驱动图像融合发现了S黄色葡萄球菌赖氨酰磷脂酰甘油脂质,定位于受感染组织内的选定细菌群落。赖氨酰磷脂酰甘油的缺乏与脊椎动物定植期间致病性降低有关,因为这些脂质提供针对先天免疫系统的保护。鼠类和人类感染中存在不同的葡萄球菌赖氨酰磷脂酰甘油分布,表明微生物对宿主防御存在异质的、空间定向的反应。

更新日期:2022-06-01
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