Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Appl Environ Microbiol. 2018 Mar 1;84(6). doi: 10.1128/AEM.02575-17. Print 2018 Mar 15.
Secondary metabolites are an important source of pharmaceuticals and key modulators of microbe-microbe interactions. The bacterium is part of the family of eubacteria and produces a number of biologically active secondary metabolites. In this study, we screened for novel regulators of secondary metabolites synthesized by a clinical isolate of and found mutations in a gene for an uncharacterized UmoB/IgaA family member here named Mutation of conferred a severe loss of the secondary metabolites prodigiosin and serratamolide. The mutation conferred pleiotropic phenotypes, including altered biofilm formation, highly increased capsular polysaccharide production, and loss of swimming and swarming motility. These phenotypes corresponded to transcriptional changes in , , and Unlike other UmoB/IgaA family members, was found to be not essential for growth in , yet from , from , and an uncharacterized predicted ortholog from complemented the mutant secondary metabolite defects, suggesting highly conserved function. These data support the idea that UmoB/IgaA family proteins are functionally conserved and extend the known regulatory influence of UmoB/IgaA family proteins to the control of competition-associated secondary metabolites and biofilm formation. IgaA/UmoB family proteins are found in members of the family of bacteria, which are of environmental and public health importance. IgaA/UmoB family proteins are thought to be inner membrane proteins that report extracellular stresses to intracellular signaling pathways that respond to environmental challenge. This study introduces a new member of the IgaA/UmoB family and demonstrates a high degree of functional similarity between IgaA/UmoB family proteins. Moreover, this study extends the phenomena controlled by IgaA/UmoB family proteins to include the biosynthesis of antimicrobial secondary metabolites.
次生代谢物是药物的重要来源，也是微生物-微生物相互作用的关键调节剂。该细菌是真细菌科的一部分，能产生许多具有生物活性的次生代谢物。在这项研究中，我们筛选了一种临床分离株 中合成的次生代谢物的新型调节剂，发现了一个未被描述的 UmoB/IgaA 家族成员的基因突变，在这里我们将其命名为 突变导致次级代谢产物灵菌红素和蛇孢菌素的严重缺失。该 突变赋予了多种表型，包括改变生物膜形成、高度增加荚膜多糖产生以及丧失游泳和群集运动能力。这些表型与 中的转录变化相对应， 、 和 与其他 UmoB/IgaA 家族成员不同，发现 对于 在 中的生长不是必需的，然而， 来自 ， 来自 ，和一个未被描述的预测同源物从 补充了 突变体次生代谢物缺陷，表明高度保守的功能。这些数据支持了 UmoB/IgaA 家族蛋白在功能上保守的观点，并将 UmoB/IgaA 家族蛋白的已知调控作用扩展到了竞争相关次生代谢物和生物膜形成的控制。IgaA/UmoB 家族蛋白存在于具有环境和公共卫生重要性的细菌的 科成员中。IgaA/UmoB 家族蛋白被认为是一种内膜蛋白，它将细胞外应激报告给细胞内信号通路，以响应环境挑战。本研究介绍了 IgaA/UmoB 家族的一个新成员，并证明了 IgaA/UmoB 家族蛋白之间具有高度的功能相似性。此外，本研究将 IgaA/UmoB 家族蛋白控制的现象扩展到包括抗菌次生代谢物的生物合成。
