Shigella flexneri utilizes intestinal signals to control its virulence.
Shigella flexneri utilizes intestinal signals to control its virulence.
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DOI：
10.1080/19490976.2023.2256767
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发表时间：
2023-12
期刊：
影响因子：
12.2
通讯作者：
中科院分区：
文献类型：
--
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肠道病原体已经进化到利用周围环境的元素来优化其感染策略。实现这一目标的常见机制是利用肠道化合物作为信号来控制毒力主调节剂的活性。弗氏志贺氏菌（S.flexneri）是一种高度传染性的肠侵袭性病原体，只需很少的微生物即可引起结肠粘膜的侵袭。入侵程序由毒力主调节器 VirF 控制。在这里，我们表明，福氏链球菌可以利用结肠中常见的脂肪酸来抑制其毒力，使其能够大力支持其增殖，从而增加其致病性。研究表明，油酸、棕榈油酸和顺式-2-十六烯酸等结肠脂肪酸可直接与 VirF 结合并介导其迅速降解。这些脂肪酸还破坏了 VirF 与其靶 DNA 结合的能力，抑制下游毒力基因的转录，并显着减少福氏链球菌对结肠上皮细胞的侵袭。仅在入侵诱导条件下，用结肠脂肪酸处理才显着增加病原体的生长速率，这表明毒力负担的减少促进了生长优势。这些结果证明了福氏志贺氏菌利用肠道化合物作为信号来增加其首选入侵部位数量的过程，强调了尽管感染剂量极小但仍能实现全谱志贺氏菌病的机制。这凸显了弗氏链霉菌为了最大限度地发挥致病效益而进行的环境适应的优雅模式。
The enteric pathogens have evolved to utilize elements from their surroundings to optimize their infection strategies. A common mechanism to achieve this is to employ intestinal compounds as signals to control the activity of a master regulator of virulence. Shigella flexneri (S. flexneri) is a highly infectious entero-invasive pathogen which requires very few organisms to cause invasion of the colonic mucosa. The invasion program is controlled by the virulence master regulator VirF. Here, we show that the fatty acids commonly found in the colon can be exploited by S. flexneri to repress its virulence, allowing it to energetically finance its proliferation, thus increasing its pathogenicity. Colonic fatty acids such as oleic, palmitoleic and cis-2-hexadecenoic acid were shown to directly bind to VirF and mediate its prompt degradation. These fatty acids also disrupted the ability of VirF to bind to its target DNA, suppressing the transcription of the downstream virulence genes and significantly reducing the invasion of S. flexneri to colonic epithelial cells. Treatment with colonic fatty acids significantly increased the growth rate of the pathogen only under invasion-inducing conditions, showing that the reduction in the burden of virulence promotes a growth advantage. These results demonstrate the process by which S. flexneri can employ intestinal compounds as signals to increase its numbers at its preferred site of invasion, highlighting the mechanism by which the full spectrum of shigellosis is achieved despite a miniscule infectious dose. This highlights an elegant model of environmental adaption by S. flexneri to maximize the pathogenic benefit.
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