Fatty acids can inhibit Staphylococcus aureus SaeS activity at the membrane independent of alterations in respiration.

Fatty acids can inhibit Staphylococcus aureus SaeS activity at the membrane independent of alterations in respiration.
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DOI:
10.1111/mmi.14830
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发表时间:
2021-11
影响因子:
3.6
通讯作者:
Bose JL
Bose JL
中科院分区:
生物学2区
文献类型:
--
作者:
DeMars ZR;Krute CN;Ridder MJ;Gilchrist AK;Menjivar C;Bose JL

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在金黄色葡萄球菌中,双组分系统SaeRS负责调节该病原体成功所必需的各种毒力因子。SaeRS可以被嗜酸乳杆菌衍生的产物刺激,但最近也显示出被游离脂肪酸灭活。尚未描述脂肪酸如何负面影响SaeRS的机制。我们发现,不饱和脂肪酸,以及脂肪酸不常见于葡萄球菌膜,防止激活SaeRS在一个较低的浓度比他们的饱和对应物。这些脂肪酸可以对SaeRS产生负面影响,而不会改变细菌的呼吸能力。为了揭示脂肪酸如何影响SaeRS功能/活性的潜在机制,我们利用了在S.金黄色葡萄球菌以及嵌合SaeS蛋白。使用这些工具,我们确定了天然的跨膜结构域的SaeS支配的转录反应的脂肪酸在S。金黄色。我们的数据支持一个模型,其中游离脂肪酸直接通过传感器激酶SaeS改变双组分系统SaeRS的活性,并且依赖于蛋白质的跨膜结构域。脂肪酸可以抑制SaeS活性,不饱和脂肪酸通常是比饱和脂肪酸更强的抑制剂。这种抑制发生在膜上,并且不依赖于SaeP、SaeQ和呼吸活性的变化,但需要天然的SaeS跨膜结构域。
In Staphylococcus aureus, the two-component system SaeRS is responsible for regulating various virulence factors essential for the success of this pathogen. SaeRS can be stimulated by neutrophil-derived products but has also recently been shown to be inactivated by the presence of free fatty acids. A mechanism for how fatty acids negatively impacts SaeRS has not been described. We found that unsaturated fatty acids, as well as fatty acids not commonly found in Staphylococcal membranes, prevent the activation of SaeRS at a lower concentration than their saturated counterparts. These fatty acids can negatively impact SaeRS without altering the respiratory capacity of the bacterium. To uncover a potential mechanism for how fatty acids impact SaeRS function/activity, we utilized a naturally occurring point mutation found in S. aureus as well as chimeric SaeS proteins. Using these tools, we identified that the native transmembrane domains of SaeS dictate the transcriptional response to fatty acids in S. aureus. Our data support a model where free fatty acids alter the activity of the two-component system SaeRS directly through the sensor kinase SaeS and is dependent on the transmembrane domains of the protein. Fatty acid can inhibit SaeS activity with unsaturated fatty acids generally being stronger inhibitors than saturated fatty acids. This suppression occurs at the membrane and is independent of SaeP, SaeQ, and changes in respiratory activity, but requires the native SaeS transmembrane domains.
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