A newly identified bacterial cell-penetrating peptide that reduces the transcription of pro-inflammatory cytokines.

Cell-permeable proteins, also called cell-penetrating peptides (CPPs), have the ability to cross cellular membranes, either alone or in association with bioactive cargo. We identified the Yersinia protein YopM as a novel bacterial cell-permeable protein. Here, we describe the ability of isolated recombinant YopM to enter host cells without a requirement for additional factors. This autonomous translocation of YopM was confirmed in several cell types, indicating that it is an intrinsic property of YopM. Using truncated versions of YopM, we show that either of the two N-terminal alpha-helices of YopM mediates translocation into the cells. Furthermore, the two alpha-helices are also able to deliver heterologous cargo, such as GFP or YopE. In addition, we found that, after entering the cells, YopM is functional and efficiently downregulates the transcription of pro-inflammatory cytokines (such as tumor necrosis factor-alpha and interleukins 12, 15 and 18). This finding suggests the potential use of YopM as a tool for protein delivery. Furthermore, it can lead to important advances in understanding and evaluating the intracellular and molecular function of YopM without the need for infection with Yersinia.