SarS and Rot are necessary for the repression of lukED and lukSF-PV in Staphylococcus aureus.
SarS and Rot are necessary for the repression of lukED and lukSF-PV in Staphylococcus aureus.
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DOI：
10.1128/spectrum.01656-23
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发表时间：
2023-12-12
影响因子：
3.7
通讯作者：
Torres, Victor J.
中科院分区：
文献类型：
--
作者：
Anderson, Exene E.;Ilmain, Juliana K.;Torres, Victor J.
金黄色葡萄球菌是一种机会性病原体，它利用一系列不同的毒力因子来逃避免疫系统。双组分成孔杀白素对于它们靶向和杀死吞噬细胞的能力特别重要。其中两种毒素LukED和LukSF-PV的操纵子受到SARS和Rot两种蛋白质的抑制。然而，这些抑制物是如何共同作用来抑制这些毒素的，目前还不完全清楚。在这里，我们确定SARS和Rot对杀白素的抑制不是相加的，而且SARS和Rot能够同时与杀白素启动子结合。此外，在使用原代人类中性粒细胞的组织培养模型中，与单一缺失SARS和ROT相比，两个抑制子的缺失并不会导致毒力增加。进一步的实验表明，在体内小鼠感染模型中，缺乏一个抑制子的菌株对两个抑制子的毒力相似。总体而言，这些数据表明，虽然SARS和Rot对杀白素的抑制不是相加的，但这两种蛋白质对这些毒素的抑制是关键的。杀白素在解除宿主免疫系统的武装和促进感染方面发挥着重要作用。虽然SARS和Rot都被确定为杀白素的抑制物，但每个抑制物在感染中的重要性尚不清楚。在这里，我们证明了SARS和Rot的抑制不是相加的，并且表明除了上调彼此的表达外，它们还能够同时与杀白素启动子结合。这些发现表明，这两个抑制子都是最大限度地抑制LukED和LukSF-PV所必需的，并阐明了金黄色葡萄球菌毒力调节因子之间的另一种复杂关系。
Staphylococcus aureus is an opportunistic pathogen that employs an array of different virulence factors to evade the immune system. The bi-component pore-forming leukocidins are of particular importance for their ability to target and kill phagocytes. The operon of two of these toxins, lukED and lukSF-PV, are repressed by two proteins, SarS and Rot. However, how these repressors work together to repress these toxins is not completely understood. Here, we determine that repression of leukocidins by SarS and Rot is not additive and that SarS and Rot are able to bind concurrently to the leukocidin promoters. In addition, in a tissue culture model using primary human neutrophils, the deletion of both repressors did not result in increased virulence compared to the single deletions of sarS and rot. Further experiments revealed that in an in vivo mouse infection model, virulence was similar in strains lacking one versus both repressors. Overall, these data show that while the repression of leukocidins by SarS and Rot is not additive, both proteins are critical for the repression of these toxins. The leukocidins play an important role in disarming the host immune system and promoting infection. While both SarS and Rot have been established as repressors of leukocidins, the importance of each repressor in infection is unclear. Here, we demonstrate that repression by SarS and Rot is not additive and show that in addition to upregulating expression of each other, they are also able to bind concurrently to the leukocidin promoters. These findings suggest that both repressors are necessary for maximal repression of lukED and lukSF-PV and illuminate another complex relationship among Staphylococcus aureus virulence regulators.
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