Pseudomonas aeruginosa Exotoxin A (ETA) (ETA)

Pseudomonas aeruginosa Exotoxin A (ETA), frequently referred to as Exoprotein A, is a potent 66 kDa virulence factor secreted by the bacterium Pseudomonas aeruginosa [1]. It belongs to the family of mono-ADP-ribosyltransferases and acts by modifying eukaryotic elongation factor 2 (eEF-2), which irreversibly shuts down host cell protein synthesis and triggers apoptosis [2]. In the pharmaceutical industry, a detoxified version of this protein, recombinant Exoprotein A (rEPA), is widely utilized as a carrier protein in conjugate vaccines to enhance the immunogenicity of bacterial polysaccharides by recruiting T-cell help [5]. Additionally, fragments of the toxin are used as cytotoxic payloads in recombinant immunotoxins, such as moxetumomab pasudotox, which target specific cancer cell surface markers to deliver the toxin directly to the cytoplasm of malignant cells [3, 4]. The protein's ability to be produced recombinantly and its well-characterized structure make it a versatile tool in both prophylactic and therapeutic drug development [2, 4]. However, its use is associated with specific safety challenges, including potential off-target toxicity and the development of neutralizing antibodies in patients [3, 4].

Other names

Exoprotein AEPArEPAPseudomonas exotoxinPEPEAExotoxin A

Pseudomonas aeruginosa Exotoxin A acts as an ADP-ribosyltransferase that covalently attaches an ADP-ribose moiety from NAD+ to a modified histidine residue (diphthamide) on eukaryotic elongation factor 2 (eEF-2) [1, 2]. This modification inactivates eEF-2, leading to the total inhibition of protein synthesis and subsequent cell death via apoptosis [2]. When used as a carrier protein in conjugate vaccines, it provides foreign T-cell epitopes that are processed and presented by MHC class II molecules, stimulating T-helper cells to facilitate B-cell isotype switching and memory formation against the conjugated polysaccharide antigen [5].