Lin Tien-Huang, Tseng Cheng-Yin, Lai Yi-Chyi, Wu Chien-Chen, Huang Chun-Fa, Lin Ching-Ting
Division of Urology, Taichung Tzu Chi General Hospital, The Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.
School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan.
Front Microbiol. 2017 Oct 16;8:1984. doi: 10.3389/fmicb.2017.01984. eCollection 2017.
In , we have previously shown that IscR, an Fe-S cluster-containing transcriptional factor, plays a dual role in controlling capsular polysaccharide biosynthesis and iron-acquisition systems by switching between its holo and apo forms. In this study, the effect of IscR on type 3 fimbriae expression and biofilm formation was investigated. We found that production of the major subunit of type 3 fimbriae, MrkA, was increased in the Δ and strains, a strain expressing a mutant IscR that mimics apo-IscR, at both the translational and transcriptional levels. Based on the fact that type 3 fimbriae expression is the major factor affecting biofilm formation, increased biofilm formation was also found in Δ or , suggesting that holo-IscR represses biofilm formation. However, the repression of type 3 fimbriae expression by IscR is indirect. To further understand the regulatory mechanism of IscR, the effect of IscR on the expression of , which encodes cyclic di-GMP (c-di-GMP)-related regulatory proteins that control type 3 fimbriae expression, was studied. We found that holo-IscR could directly repress transcription, indicating that MrkHI is required for IscR regulation of type 3 fimbriae expression. Finally, deletion of attenuated virulence in a peritonitis model of mouse infection, while the absence of the [2Fe-2S] cluster of IscR had no effect on virulence during infection. Taken together, our results demonstrate the underlying mechanism of the [2Fe-2S] cluster of IscR in controlling type 3 fimbriae expression and its effect on pathogenesis.
在之前的研究中，我们已经表明，含Fe-S簇的转录因子IscR通过在其全酶和脱辅基形式之间切换，在控制荚膜多糖生物合成和铁获取系统中发挥双重作用。在本研究中，研究了IscR对3型菌毛表达和生物膜形成的影响。我们发现，在Δ和菌株（一种表达模拟脱辅基IscR的突变IscR的菌株）中，3型菌毛主要亚基MrkA的产生在翻译和转录水平上均增加。基于3型菌毛表达是影响生物膜形成的主要因素这一事实，在Δ或中也发现生物膜形成增加，这表明全酶形式的IscR抑制生物膜形成。然而，IscR对3型菌毛表达的抑制是间接的。为了进一步了解IscR的调控机制，研究了IscR对编码控制3型菌毛表达的环二鸟苷（c-di-GMP）相关调节蛋白的基因的表达的影响。我们发现全酶形式的IscR可以直接抑制该基因的转录，表明MrkHI是IscR调节3型菌毛表达所必需的。最后，在小鼠感染腹膜炎模型中，该基因的缺失减弱了菌株的毒力，而IscR的[2Fe-2S]簇缺失对感染期间菌株的毒力没有影响。综上所述，我们的结果证明了IscR的[2Fe-2S]簇在控制3型菌毛表达中的潜在机制及其对菌株致病性的影响。
