AraC-type regulators HilC and RtsA are directly controlled by an intestinal fatty acid to regulate Salmonella invasion.
AraC-type regulators HilC and RtsA are directly controlled by an intestinal fatty acid to regulate Salmonella invasion.
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DOI：
10.1111/mmi.14835
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发表时间：
2021-12
影响因子：
3.6
通讯作者：
Altier C
中科院分区：
文献类型：
--
作者：
Chowdhury R;Pavinski Bitar PD;Adams MC;Chappie JS;Altier C
肠上皮细胞的入侵是一个必要的，但能量昂贵的生存策略，因此，严格利用特定的线索从环境调节。肠道病原体沙门氏菌通过三种AraC型转录激活因子HilD、HilC和RtsA的巧妙协调来控制其入侵机制。大多数环境信号靶向HilD以控制入侵，而HilC和RtsA已知仅增强这些对HilD的影响。在这里，我们表明，在小鼠结肠中发现的脂肪酸，顺式-2-十六碳烯酸（c2-HDA），抑制沙门氏菌的入侵，直接针对HilC和RtsA，除了HilD。c2-HDA直接结合这些调节因子中的每一种，并抑制它们与DNA靶的附着，即使在没有HilD的情况下也抑制侵袭。然而，与HilD不同，脂肪酸结合不影响HilC和RtsA蛋白的稳定性。重要的是，我们表明，HilC和RtsA是非常有效的恢复HilD生产和入侵基因表达后，消除抑制性脂肪酸c2-HDA。总之，这些结果阐明了一种精确的机制，通过这种机制，HilC和RtsA可以调节沙门氏菌在肠道不同区域的侵袭，有助于我们了解这种肠道病原体如何感知和适应不同的肠道环境，同时保持其毒力。沙门氏菌已经进化到表达和抑制其入侵机制，以响应其在肠道中位置的化学组成。在这里，我们展示了入侵调节因子HilC和RtsA如何帮助沙门氏菌利用肠道中存在的化学信号来抑制和恢复其毒力，并扩大这些蛋白质在沙门氏菌致病性调节中的作用。
Invasion of the intestinal epithelium is an essential but energetically expensive survival strategy and is therefore tightly regulated by utilizing specific cues from the environment. The enteric pathogen Salmonella controls its invasion machinery through the elegant coordination of three AraC-type transcription activators, HilD, HilC and RtsA. Most environmental signals target HilD to control invasion, whereas HilC and RtsA are known only to augment these effects on HilD. Here we show that a fatty acid found in the murine colon, cis-2-hexadecenoic acid (c2-HDA), represses Salmonella invasion by directly targeting HilC and RtsA, in addition to HilD. c2-HDA directly binds each of these regulators and inhibits their attachment to DNA targets, repressing invasion even in the absence of HilD. Fatty acid binding, however, does not affect HilC and RtsA protein stability, unlike HilD. Importantly, we show that HilC and RtsA are highly effective in restoring HilD production and invasion gene expression after elimination of the repressive fatty acid c2-HDA. Together, these results illuminate a precise mechanism by which HilC and RtsA may modulate invasion as Salmonella navigates through different regions of the intestine, contributing to our understanding of how this enteric pathogen senses and adapts to a diverse intestinal environment while maintaining its virulence. Salmonella has evolved to express and repress its invasion machinery in response to the chemical composition of its location in the intestine. Here we show how the invasion regulators HilC and RtsA help Salmonella to utilize chemical signals present in the intestine to repress and reinstate its virulence and expand the roles of these proteins in the regulation of Salmonella’s pathogenicity.
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影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
影响因子：
4.1
作者：
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影响因子：
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作者：
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通讯作者：
Lindow S
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL