Salmonella Invasion Is Controlled by Competition among Intestinal Chemical Signals.
Salmonella Invasion Is Controlled by Competition among Intestinal Chemical Signals.
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DOI：
10.1128/mbio.00012-23
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发表时间：
2023-04-25
期刊：
影响因子：
6.4
通讯作者：
Altier, Craig
中科院分区：
文献类型：
--
作者：
Chowdhury, Rimi;Bitar, Paulina Pavinski D.;Chapman, Hanora M.;Altier, Craig
关键词：
肠道是一个复杂、不断变化的环境，充满了一系列信号分子。为了在这样一个复杂的器官中定殖，病原体已经适应利用当地环境的特定线索来复杂地调节其毒力决定子的表达。沙门氏菌优先定植于远端回肠，这是一个富含代谢物甲酸的生态位。在这里，我们表明，这种代谢物在回肠远端的浓度相对较高，可以防止其他信号抑制沙门氏菌在该区域的入侵。我们发现，输入的和未代谢的甲酸作为细胞质信号，竞争性地与沙门氏菌入侵的主要转录调节因子 HilD 结合，从而防止抑制性脂肪酸与蛋白质结合。这导致 HilD 寿命延长，并随后抑制入侵基因。这项研究证明了沙门氏菌利用肠道信号之间的竞争来发挥其作为病原体优势的重要机制。
The intestine is a complex, ever-changing environment replete with an array of signaling molecules. To colonize such a complex organ, pathogens have adapted to utilize specific cues from the local environment to intricately regulate the expression of their virulence determinants. Salmonella preferentially colonizes the distal ileum, a niche enriched in the metabolite formic acid. Here, we show that the relatively higher concentration of this metabolite in the distal ileum prevents other signals from repressing Salmonella invasion in that region. We show that imported and unmetabolized formic acid functions as a cytoplasmic signal that competitively binds to HilD, the master transcriptional regulator of Salmonella invasion, thus preventing repressive fatty acids from binding to the protein. This results in an increased lifetime of HilD and subsequent derepression of invasion genes. This study demonstrates an important mechanism by which Salmonella utilizes competition among signals in the gut to its advantage as a pathogen.
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