CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
Academy of Scientific and Innovative Research, Ghaziabad, India.
Infect Immun. 2018 May 22;86(6). doi: 10.1128/IAI.00041-18. Print 2018 Jun.
, a successful human pathogen, utilizes multiple carbon sources from the host but adapts to a fatty-acid-rich environment We sought to delineate the physiologic response of to a lipid-rich environment by using differentiated adipocytes as a model system. Global transcriptome profiling based on RNA sequencing was performed for bacilli from infected adipocytes and preadipocytes. Genes involved in fatty acid synthesis were downregulated, while those predicted to be involved in triglyceride biosynthesis were upregulated, in bacilli isolated from adipocytes, indicating reliance on host-derived fatty acids. Transcription factor network analysis indicated suppression of IdeR-regulated genes, suggesting decreased iron uptake by in the adipocyte model. This suppression of iron uptake coincided with higher ferritin and iron levels in adipocytes than in preadipocytes. In accord with the role of iron in mediating oxidative stress, we observed upregulation of genes involved in mitigating oxidative stress in isolated from adipocytes. We provide evidence that oleic acid, a major host-derived fatty acid, helps reduce the bacterial cytoplasm, thereby providing a safe haven for an mutant that is sensitive to iron-mediated oxidative stress. Via an independent mechanism, host ferritin is also able to rescue the growth of this mutant. Our work highlights the inherent synergy between macronutrients and micronutrients of the host environment that converge to provide resilience to the pathogen. This complex synergy afforded by the adipocyte model of infection will aid in the identification of genes required by in a caseous host environment.
金黄色葡萄球菌是一种成功的人类病原体，它可以利用宿主提供的多种碳源，但它能够适应富含脂肪酸的环境。我们试图通过使用分化的脂肪细胞作为模型系统来描绘金黄色葡萄球菌对富含脂质环境的生理反应。基于 RNA 测序的全转录组谱分析是针对感染脂肪细胞和前脂肪细胞的杆菌进行的。从脂肪细胞中分离出的杆菌中，与脂肪酸合成相关的基因下调，而与甘油三酯生物合成相关的基因上调，这表明它们依赖于宿主来源的脂肪酸。转录因子网络分析表明 IdeR 调节基因受到抑制，表明金黄色葡萄球菌在脂肪细胞模型中减少了铁的摄取。这种铁摄取的抑制与脂肪细胞中的铁蛋白和铁水平高于前脂肪细胞相一致。与铁在介导氧化应激中的作用一致，我们观察到从脂肪细胞中分离出的金黄色葡萄球菌中与减轻氧化应激相关的基因上调。我们提供的证据表明，油酸是一种主要的宿主衍生脂肪酸，有助于减少细菌细胞质，从而为对铁介导的氧化应激敏感的金黄色葡萄球菌突变体提供一个安全的避难所。通过独立的机制，宿主铁蛋白也能够拯救该突变体的生长。我们的工作强调了宿主环境中的宏量营养素和微量营养素之间固有的协同作用，这些协同作用共同为病原体提供了弹性。这种感染脂肪细胞模型所提供的复杂协同作用将有助于确定在干酪样宿主环境中金黄色葡萄球菌所需的基因。
