Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, North Carolina, USA.
mBio. 2020 Apr 14;11(2):e00112-20. doi: 10.1128/mBio.00112-20.
can colonize the human host and cause a variety of superficial and invasive infections. The success of as a pathogen derives from its ability to modulate its virulence through the release, sensing of and response to cyclic signaling peptides. Here we provide, for the first time, evidence that processes and secretes small linear peptides through a specialized pathway that converts a lipoprotein leader into an extracellular peptide signal. We have identified and confirmed the machinery for each step and demonstrate that the putative membrane metalloprotease Eep and the EcsAB transporter are required to complete the processing and secretion of the peptides. In addition, we have identified several linear peptides, including the interspecies signaling molecule -cAM373, that are dependent on this processing and secretion pathway. These findings are particularly important because multiple Gram-positive bacteria rely on small linear peptides to control bacterial gene expression and virulence. Here, we provide evidence indicating that secretes small linear peptides into the environment via a novel processing and secretion pathway. The discovery of a specialized pathway for the production of small linear peptides and the identification of these peptides leads to several important questions regarding their role in biology, most interestingly, their potential to act as signaling molecules. The observations in this study provide a foundation for further in-depth studies into the biological activity of small linear peptides in .
可以定植于人体宿主并引起多种浅表和侵袭性感染。作为病原体的成功源于其通过释放、感知和响应循环信号肽来调节其毒力的能力。在这里，我们首次提供证据表明，通过一种专门的途径将脂蛋白前体转化为细胞外肽信号，来加工和分泌小线性肽。我们已经鉴定并证实了每一步骤所需的机制，并证明了假定的膜金属蛋白酶 Eep 和 EcsAB 转运蛋白是完成肽加工和分泌所必需的。此外，我们还鉴定了几种线性肽，包括种间信号分子 -cAM373，它们依赖于这种加工和分泌途径。这些发现尤为重要，因为多种革兰氏阳性菌依赖于小线性肽来控制细菌基因表达和毒力。在这里，我们提供的证据表明，通过一种新的加工和分泌途径将小线性肽分泌到环境中。小线性肽产生的专门途径的发现以及这些肽的鉴定引发了关于它们在生物学中的作用的几个重要问题，最有趣的是，它们作为信号分子的潜在作用。本研究中的观察结果为进一步深入研究小线性肽在 中的生物学活性提供了基础。
