Cytolysin A (ClyA): A Bacterial Virulence Factor with Potential Applications in Nanopore Technology, Vaccine Development, and Tumor Therapy

Abstract

Cytolysin A (ClyA) is a pore-forming toxin that is produced by some bacteria from the Enterobacteriaceae family. This review provides an overview of the current state of knowledge regarding ClyA, including the prevalence of the encoding gene and its transcriptional regulation, the secretion pathway used by the protein, and the mechanism of protein assembly, and highlights potential applications of ClyA in biotechnology. ClyA expression is regulated at the transcriptional level, primarily in response to environmental stressors, and ClyA can exist stably both as a soluble monomer and as an oligomeric membrane complex. At high concentrations, ClyA induces cytolysis, whereas at low concentrations ClyA can affect intracellular signaling. ClyA is secreted in outer membrane vesicles (OMVs), which has important implications for biotechnology applications. For example, the native pore-forming ability of ClyA suggests that it could be used as a component of nanopore-based technologies, such as sequencing platforms. ClyA has also been exploited in vaccine development owing to its ability to present antigens on the OMV surface and provoke a robust immune response. In addition, ClyA alone or OMVs carrying ClyA fusion proteins have been investigated for their potential use as anti-tumor agents.

Keywords: biotechnology application; cytolysin A; outer membrane vesicles; pore-forming toxin.

Figure 1

Schematic representation of the OMV-mediated secretion pathway for ClyA and the predicted pore assembly pathway. ClyA protein is secreted by OMVs and the monomer oligomerizes to form the active pore assemblies within OMVs in a redox state-dependent manner [20]. In the assembly process, once ClyA reaches the target membrane, the monomer first undergoes a conformational change to a protomer and then predominantly assembles into an octameric [53], 13-meric (redox state-independent) [55], or dodecameric [14] pore complex by contact with membrane lipids or the detergent, n-dodecylmaltoside (DDM).