The Stringent Response Regulator DksA Is Required for Salmonella enterica Serovar Typhimurium Growth in Minimal Medium, Motility, Biofilm Formation, and Intestinal Colonization
The Stringent Response Regulator DksA Is Required for Salmonella enterica Serovar Typhimurium Growth in Minimal Medium, Motility, Biofilm Formation, and Intestinal Colonization
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DOI：
10.1128/iai.01135-15
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发表时间：
2016-01-01
影响因子：
3.1
通讯作者：
Gal-Mor, Ohad
中科院分区：
文献类型：
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作者：
Azriel, Shalhevet;Goren, Alina;Gal-Mor, Ohad
鼠伤寒沙门氏菌是一种兼性细胞内人类和动物细菌病原体，对全世界公共卫生构成重大威胁。沙门氏菌的致病性需要多种生理和毒力途径的复杂协调。 DksA 是一种保守的革兰氏阴性调节因子，属于一组独特的转录因子，可直接与 RNA 聚合酶二级通道结合，在严格反应期间增强信号分子 ppGpp 的作用。在这里，我们确定，在鼠伤寒沙门氏菌中，dksA 在对数生长期被诱导，并且 DksA 对于在基本限定培养基中的生长至关重要，并且在运动和生物膜形成中发挥重要作用。此外，我们确定 DksA 正向调节沙门氏菌致病岛 1 和运动趋化基因，并且对于鼠伤寒沙门氏菌侵入人上皮细胞和被巨噬细胞摄取是必需的。相反，DksA被发现对于鼠伤寒沙门氏菌宿主细胞粘附来说是可有可无的。最后，利用结肠炎小鼠模型，我们发现dksA在感染早期在盲肠中部空间诱导，并且是胃肠道定植和体内全身感染所必需的。总而言之，这些数据表明祖先严格反应调节剂 DksA 协调各种生理和毒力鼠伤寒沙门氏菌程序，因此是沙门氏菌的关键毒力调节剂。
Salmonella enterica serovar Typhimurium is a facultative intracellular human and animal bacterial pathogen posing a major threat to public health worldwide. Salmonella pathogenicity requires complex coordination of multiple physiological and virulence pathways. DksA is a conserved Gram-negative regulator that belongs to a distinct group of transcription factors that bind directly to the RNA polymerase secondary channel, potentiating the effect of the signaling molecule ppGpp during a stringent response. Here, we established that in S. Typhimurium, dksA is induced during the logarithmic phase and DksA is essential for growth in minimal defined medium and plays an important role in motility and biofilm formation. Furthermore, we determined that DksA positively regulates the Salmonella pathogenicity island 1 and motility-chemotaxis genes and is necessary for S. Typhimurium invasion of human epithelial cells and uptake by macrophages. In contrast, DksA was found to be dispensable for S. Typhimurium host cell adhesion. Finally, using the colitis mouse model, we found that dksA is spatially induced at the midcecum during the early stage of the infection and required for gastrointestinal colonization and systemic infection in vivo. Taken together, these data indicate that the ancestral stringent response regulator DksA coordinates various physiological and virulence S. Typhimurium programs and therefore is a key virulence regulator of Salmonella.