Linoleic Acid Stimulation of WT Staphylococcus aureus USA300 NRS384. Staphylococcus aureus USA300-0114

Methicillin-resistant Staphylococcus aureus (MRSA) infections result in more than 200,000 hospitalizations and 10,000 deaths in the United States each year and remain an important medical challenge. A key factor of S. aureus pathogenesis is the production of virulence proteins that are secreted into the extracellular matrix damaging host tissues and forming abscesses that may serve as replicative niches for the bacteria. We recently discovered that host-derived cis-unsaturated fatty acids activate the transcription and translation of EsxA, a protein that plays a central role in abscess formation in clinically relevant MRSA strains. Additionally, we discovered that fatty acid stimulation of EsxA is dependent on fakA, a gene that encodes a protein responsible for the incorporation of exogenous fatty acids into the S. aureus phospholipid membrane. In order to gain a comprehensive understanding of host-fatty-acid-sensing in S. aureus, we performed RNA-Seq analysis on WT Staphylococcus aureus USA300 NRS384, a community-acquired MRSA strain, in the presence and absence of 10μM linoleic acid. Overall design: RNA-Seq analysis was performed on WT Staphylococcus aureus USA300 NRS384 in the presence and absence of 10μM linoleic acid. Each condition was performed in triplicate thereby yielding a total of 6 samples for RNA-Seq analysis.

耐甲氧西林金黄色葡萄球菌（Methicillin-resistant Staphylococcus aureus, MRSA）感染每年在美国导致超过20万例住院病例与1万例死亡，至今仍是亟待解决的重大医学难题。金黄色葡萄球菌致病机制的核心环节之一，是分泌毒力蛋白至细胞外基质，破坏宿主组织并形成脓肿——此类脓肿可作为细菌的复制微环境。我们近期研究发现，宿主源性顺式不饱和脂肪酸可激活EsxA的转录与翻译过程；该蛋白在临床相关MRSA菌株的脓肿形成过程中发挥核心调控作用。此外，我们还证实，脂肪酸对EsxA的调控作用依赖于fakA基因：该基因编码的蛋白负责将外源性脂肪酸整合至金黄色葡萄球菌的磷脂膜中。为全面解析金黄色葡萄球菌对宿主脂肪酸的感知机制，我们以社区获得性MRSA菌株野生型金黄色葡萄球菌USA300 NRS384为研究对象，分别在添加10μM亚油酸与不添加亚油酸的条件下开展RNA测序（RNA-Seq）分析。整体实验设计如下：对上述两种培养条件，每组均设置3次生物学重复，总计获得6份用于RNA-Seq分析的样本。