Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
mBio. 2021 Mar 9;12(2):e03303-20. doi: 10.1128/mBio.03303-20.
Quorum sensing is a process of cell-to-cell communication that bacteria use to orchestrate collective behaviors. Quorum sensing depends on the production, release, and detection of extracellular signal molecules called autoinducers (AIs) that accumulate with increasing cell density. While most AIs are species specific, the AI called AI-2 is produced and detected by diverse bacterial species, and it mediates interspecies communication. We recently reported that mammalian cells produce an AI-2 mimic that can be detected by bacteria through the AI-2 receptor LuxP, potentially expanding the role of the AI-2 system to interdomain communication. Here, we describe a second molecule capable of interdomain signaling through LuxP, 4-hydroxy-5-methylfuran-3(2H)-one (MHF), that is produced by the yeast Screening the deletion collection revealed Cff1p, a protein with no known role, to be required for MHF production. Cff1p is proposed to be an enzyme, with structural similarity to sugar isomerases and epimerases, and substitution at the putative catalytic residue eliminated MHF production in Sequence analysis uncovered Cff1p homologs in many species, primarily bacterial and fungal, but also viral, archaeal, and higher eukaryotic. Cff1p homologs from organisms from all domains can complement a mutant and restore MHF production. In all cases tested, the identified catalytic residue is conserved and required for MHF to be produced. These findings increase the scope of possibilities for interdomain interactions via AI-2 and AI-2 mimics, highlighting the breadth of molecules and organisms that could participate in quorum sensing. Quorum sensing is a cell-to-cell communication process that bacteria use to monitor local population density. Quorum sensing relies on extracellular signal molecules called autoinducers (AIs). One AI called AI-2 is broadly made by bacteria and used for interspecies communication. Here, we describe a eukaryotic AI-2 mimic, 4-hydroxy-5-methylfuran-3(2H)-one, (MHF), that is made by the yeast , and we identify the Cff1p protein as essential for MHF production. Hundreds of viral, archaeal, bacterial, and eukaryotic organisms possess Cff1p homologs. This finding, combined with our results showing that homologs from all domains can replace Cff1p, suggests that like AI-2, MHF is widely produced. Our results expand the breadth of organisms that may participate in quorum-sensing-mediated interactions.
群体感应是一种细胞间通讯的过程，细菌利用它来协调集体行为。群体感应依赖于细胞外信号分子的产生、释放和检测，这些信号分子被称为自诱导物 (autoinducers, AIs)，它们随着细胞密度的增加而积累。虽然大多数 AIs 是物种特异性的，但称为 AI-2 的 AI 是由多种细菌产生和检测的，它介导种间通讯。我们最近报道称，哺乳动物细胞产生一种 AI-2 模拟物，细菌可以通过 AI-2 受体 LuxP 检测到，这可能将 AI-2 系统的作用扩展到域间通讯。在这里，我们描述了第二种能够通过 LuxP 进行域间信号传递的分子，4-羟基-5-甲基-2(氢)-呋喃酮 (MHF)，它由酵母 筛选 缺失文库揭示 Cff1p，一种没有已知作用的蛋白质，是 MHF 产生所必需的。Cff1p 被提议为一种酶，具有与糖异构酶和差向异构酶相似的结构，在假定的催化残基处取代消除了 MHF 的产生 序列分析揭示了许多物种中的 Cff1p 同源物，主要是细菌和真菌，但也有病毒、古细菌和高等真核生物。来自所有领域的生物体的 Cff1p 同源物可以互补 突变体并恢复 MHF 的产生。在所有测试的情况下，鉴定的催化残基保守且必需产生 MHF。这些发现增加了通过 AI-2 和 AI-2 模拟物进行域间相互作用的可能性，突出了可能参与群体感应的分子和生物体的广泛范围。群体感应是一种细菌用来监测局部种群密度的细胞间通讯过程。群体感应依赖于称为自诱导物 (autoinducers, AIs) 的细胞外信号分子。一种称为 AI-2 的 AI 被广泛地由细菌产生并用于种间通讯。在这里，我们描述了一种真核 AI-2 模拟物，4-羟基-5-甲基-2(氢)-呋喃酮 (MHF)，它由酵母 产生，我们确定 Cff1p 蛋白是 MHF 产生所必需的。数以百计的病毒、古细菌、细菌和真核生物都拥有 Cff1p 同源物。这一发现，加上我们的结果表明所有领域的同源物都可以替代 Cff1p，表明像 AI-2 一样，MHF 被广泛产生。我们的结果扩大了可能参与群体感应介导相互作用的生物体范围。
