Longitudinal proliferation mapping in vivo reveals NADPH oxidase-mediated dampening of Staphylococcus aureus growth rates within neutrophils
Longitudinal proliferation mapping in vivo reveals NADPH oxidase-mediated dampening of Staphylococcus aureus growth rates within neutrophils
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DOI：
10.1038/s41598-019-42129-6
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发表时间：
2019-04-05
影响因子：
4.6
通讯作者：
Mueller, Andreas J.
中科院分区：
文献类型：
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作者：
Seiss, Elena A.;Krone, Anna;Mueller, Andreas J.
在炎症反应发生时，细菌病原体面临着改变的组织微环境，这可能严重影响其代谢活性和生长。然而，这些参数的变化仍然难以分析，这对于剖析宿主免疫反应和病原体生理学之间的相互作用至关重要。在此，我们建立了一种体内生物传感器，用于测量金黄色葡萄球菌（S。金黄色葡萄球菌）在单细胞水平上持续数天。使用活体双光子成像和定量荧光显微镜，我们表明，在中性粒细胞募集到感染部位和细菌摄取后，S。金黄色葡萄球菌增殖。这种抑制作用得到NADPH氧化酶活性的支持。因此，活性氧的产生不仅通过杀死沙门氏菌，还有助于嗜中性粒细胞内的病原体遏制。金黄色葡萄球菌，而且还通过限制细菌的生长速率。
Upon the onset of inflammatory responses, bacterial pathogens are confronted with altered tissue microenvironments which can critically impact on their metabolic activity and growth. Changes in these parameters have however remained difficult to analyze overtime, which would be critical to dissect the interplay between the host immune response and pathogen physiology. Here, we established an in vivo biosensor for measuring the growth rates of Staphylococcus aureus (S. aureus) on a single cell-level over days in an ongoing cutaneous infection. Using intravital 2-photon imaging and quantitative fluorescence microscopy, we show that upon neutrophil recruitment to the infection site and bacterial uptake, non-lethal dampening of S. aureus proliferation occurred. This inhibition was supported by NADPH oxidase activity. Therefore, reactive oxygen production contributes to pathogen containment within neutrophils not only by killing S. aureus, but also by restricting the growth rate of the bacterium.