Turbant Florian, Partouche David, El Hamoui Omar, Trépout Sylvain, Legoubey Théa, Wien Frank, Arluison Véronique
Laboratoire Léon Brillouin LLB, CEA, CNRS UMR12, Université Paris Saclay, CEA Saclay, 91191 Gif-sur-Yvette, France.
Synchrotron SOLEIL, L'Orme des Merisiers, Saint Aubin BP48, 91192 Gif-sur-Yvette, France.
Antibiotics (Basel). 2021 Mar 4;10(3):257. doi: 10.3390/antibiotics10030257.
Hfq is a bacterial regulator with key roles in gene expression. The protein notably regulates translation efficiency and RNA decay in Gram-negative bacteria, thanks to its binding to small regulatory noncoding RNAs. This property is of primary importance for bacterial adaptation and survival in hosts. Small RNAs and Hfq are, for instance, involved in the response to antibiotics. Previous work has shown that the Hfq C-terminal region (Hfq-CTR) self-assembles into an amyloid structure. It was also demonstrated that the green tea compound EpiGallo Catechin Gallate (EGCG) binds to Hfq-CTR amyloid fibrils and remodels them into nonamyloid structures. Thus, compounds that target the amyloid region of Hfq may be used as antibacterial agents. Here, we show that another compound that inhibits amyloid formation, apomorphine, may also serve as a new antibacterial. Our results provide an alternative in order to repurpose apomorphine, commonly used in the treatment of Parkinson's disease, as an antibiotic to block bacterial adaptation to treat infections.
Hfq是一种在基因表达中起关键作用的细菌调节因子。由于其与小的调节性非编码RNA结合，该蛋白在革兰氏阴性菌中显著调节翻译效率和RNA降解。这一特性对于细菌在宿主中的适应和生存至关重要。例如，小RNA和Hfq参与对抗生素的反应。先前的研究表明，Hfq的C末端区域（Hfq-CTR）自组装成淀粉样结构。还证明了绿茶化合物表没食子儿茶素没食子酸酯（EGCG）与Hfq-CTR淀粉样纤维结合并将其重塑为非淀粉样结构。因此，靶向Hfq淀粉样区域的化合物可用作抗菌剂。在此，我们表明另一种抑制淀粉样形成的化合物阿扑吗啡也可作为一种新型抗菌剂。我们的结果提供了一种选择，以便将通常用于治疗帕金森病的阿扑吗啡重新用作抗生素，以阻断细菌适应来治疗感染。
