Romero Diego, Sanabria-Valentín Edgardo, Vlamakis Hera, Kolter Roberto
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Chem Biol. 2013 Jan 24;20(1):102-10. doi: 10.1016/j.chembiol.2012.10.021.
Bacteria establish stable communities, known as biofilms, that are resistant to antimicrobials. Biofilm robustness is due to the presence of an extracellular matrix, which for several species-among them Bacillus subtilis-includes amyloid-like protein fibers. In this work, we show that B. subtilis biofilms can be a simple and reliable tool for screening of molecules with antiamyloid activity. We identified two molecules, AA-861 and parthenolide, which efficiently inhibited biofilms by preventing the formation of amyloid-like fibers. Parthenolide also disrupted pre-established biofilms. These molecules also impeded the formation of biofilms of other bacterial species that secrete amyloid proteins, such as Bacillus cereus and Escherichia coli. Furthermore, the identified molecules decreased the conversion of the yeast protein New1 to the prion state in a heterologous host, indicating the broad range of activity of the molecules.
细菌会形成稳定的群落，即生物膜，这些生物膜对抗菌剂具有抗性。生物膜的稳健性归因于细胞外基质的存在，对于包括枯草芽孢杆菌在内的多个物种而言，这种细胞外基质包含类淀粉样蛋白纤维。在这项研究中，我们表明枯草芽孢杆菌生物膜可以成为筛选具有抗淀粉样蛋白活性分子的简单且可靠的工具。我们鉴定出两种分子，AA - 861和小白菊内酯，它们通过阻止类淀粉样纤维的形成有效地抑制了生物膜。小白菊内酯还破坏了预先形成的生物膜。这些分子也阻碍了其他分泌淀粉样蛋白的细菌物种（如蜡状芽孢杆菌和大肠杆菌）生物膜的形成。此外，所鉴定的分子降低了酵母蛋白New1在异源宿主中向朊病毒状态的转化，表明这些分子具有广泛的活性范围。
