Abstract
The “Photorhabdus virulence cassettes” (PVCs) secreted by Photorhabdus are defined as “extracellular contractile injection systems” (eCISs) and can deliver effectors to eukaryotic hosts for cytotoxicity. Previously, we demonstrated the cryogenic electron microscopy (cryo-EM) structure and assembly process of an intact PVC particle from Photorhabdus asymbiotica. In this work, we characterized the biological functions of a PVC effector, which is defined as a homologous protein of Ras/Rap1-specific endopeptidase domain (RRSP) in the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin from Vibrio vulnificus. In this work, we found that the RRSP homologous protein (RRSPPa) was associated with inhibition of cell proliferation and increased cell apoptosis and death of HeLa cells. Furthermore, we discovered that RRSPPa disturbed mitotic progression, including the induction of cell cycle alteration, retardation of cell abscission time, and regression of the cleavage furrow. In addition, we revealed that RRSPPa could target the cyclin-dependent kinase 1 (CDK1) protein and block activation of CDK1 through inhibition of Thr161 phosphorylation, which partially explained the crucial role of this effector in cell mitosis.
Highlights
Contractile injection systems (CISs) are widely distributed in bacteriophages and bacteria, including the phage tail, the type VI secretion system (T6SS), the R-type pyocin, and others
We discovered an alternative function of RRSPPa in eukaryotic cells
By observing the significant decrease of viable cell number in HeLa cells producing RRSPPa, we speculated and proved that the RRSPPa was closely related to cell mitosis defects
Summary
Contractile injection systems (CISs) are widely distributed in bacteriophages and bacteria, including the phage tail, the type VI secretion system (T6SS), the R-type pyocin, and others. The main function of CISs is to deliver genetic materials and effectors into both prokaryotic and eukaryotic hosts (Taylor et al, 2018). The structure, assembly, and mechanism of typical CISs, such as the contractile tail of bacteriophage T4, have been extensively investigated. This intracellular cell puncturing nanomachine consists of an inner tube capped by a spike, a contractile sheath, and a baseplate complex located at the base of the sheath (Leiman and Shneider, 2012). Most T6SSs are located in the cytoplasm, anchored to the inner membrane, and deliver toxin effectors to eukaryotic cells or bacteria (Jani and Cotter, 2010; Russell et al, 2011)
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