Exogenous Fatty Acids Remodel Staphylococcus aureus Lipid Composition through Fatty Acid Kinase
Exogenous Fatty Acids Remodel Staphylococcus aureus Lipid Composition through Fatty Acid Kinase
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DOI：
10.1128/jb.00128-20
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发表时间：
2020-07-01
影响因子：
3.2
通讯作者：
Bose, Jeffrey L.
中科院分区：
文献类型：
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作者：
DeMars, Zachary;Singh, Vineet K.;Bose, Jeffrey L.
金黄色葡萄球菌可以利用外源脂肪酸合成磷脂。脂肪酸激酶FakA是通过磷酸化外源脂肪酸并入脂质的利用所必需的。FakA如何影响脂质膜组成尚不清楚。在这项研究中，我们使用质谱法测定了金黄色葡萄球菌在缺乏fakA的情况下的膜脂组成和性质。我们发现fakA突变体中含有较长酰基链的脂质丰度增加。由于金黄色葡萄球菌不合成不饱和脂肪酸，我们利用油酸（18:1）来追踪外源脂肪酸进入脂质。我们观察到外源脂肪酸在膜中的浓度依赖性结合需要FakA。我们还测试了FakA和外源性脂肪酸如何影响膜相关生理学，并确定了膜电位、细胞呼吸和膜流动性的变化。为了模拟宿主环境，我们对小鼠皮肤匀浆中生长的野生型和fakA突变型细菌的脂质组成进行了表征。我们发现野生型金黄色葡萄球菌可以从宿主组织中吸收外源性不饱和脂肪酸，强调了FakA在宿主皮肤组织中存在的重要性。总之，在外源脂肪酸存在的情况下，FakA对于维持磷脂膜的组成和性质很重要，影响整个细胞生理。环境脂肪酸可以用来补充内源性脂肪酸合成，以生产膜和绕过脂肪酸生物合成抑制剂。然而，无法使用这些脂肪酸是如何影响血脂的还不清楚。我们的研究结果表明，脂质组成随着脂肪酸的添加而变化，当金黄色葡萄球菌无法通过FakA激活脂肪酸时。我们确定了油酸的浓度依赖性利用，当与以前的工作相结合时，提供了脂肪酸可以作为金黄色葡萄球菌信号的证据。此外，使用小鼠皮肤匀浆作为体内条件的替代品，我们发现金黄色葡萄球菌可以结合宿主脂肪酸。这项研究强调了外源性脂肪酸如何影响细菌膜的组成和功能。
Staphylococcus aureus can utilize exogenous fatty acids for phospholipid synthesis. The fatty acid kinase FakA is essential for this utilization by phosphorylating exogenous fatty acids for incorporation into lipids. How FakA impacts the lipid membrane composition is unknown. In this study, we used mass spectrometry to determine the membrane lipid composition and properties of S. aureus in the absence of fakA. We found the fakA mutant to have increased abundance of lipids containing longer acyl chains. Since S. aureus does not synthesize unsaturated fatty acids, we utilized oleic acid (18:1) to track exogenous fatty acid incorporation into lipids. We observed a concentration-dependent incorporation of exogenous fatty acids into the membrane that required FakA. We also tested how FakA and exogenous fatty acids impact membrane-related physiology and identified changes in membrane potential, cellular respiration, and membrane fluidity. To mimic the host environment, we characterized the lipid composition of wild-type and fakA mutant bacteria grown in mouse skin homogenate. We show that wild-type S. aureus can incorporate exogenous unsaturated fatty acids from host tissue, highlighting the importance of FakA in the presence of host skin tissue. In conclusion, FakA is important for maintaining the composition and properties of the phospholipid membrane in the presence of exogenous fatty acids, impacting overall cell physiology.IMPORTANCE Environmental fatty acids can be harvested to supplement endogenous fatty acid synthesis to produce membranes and circumvent fatty acid biosynthesis inhibitors. However, how the inability to use these fatty acids impacts lipids is unclear. Our results reveal lipid composition changes in response to fatty acid addition and when S. aureus is unable to activate fatty acids through FakA. We identify concentration-dependent utilization of oleic acid that, when combined with previous work, provides evidence that fatty acids can serve as a signal to S. aureus. Furthermore, using mouse skin homogenates as a surrogate for in vivo conditions, we showed that S. aureus can incorporate host fatty acids. This study highlights how exogenous fatty acids impact bacterial membrane composition and function.