**5. Conclusion**

*E. coli* is one of the predominant species of facultative anaerobes in the human gut and in the majority of the cases is harmless to the host. These strains are mostly commensals but also contain a group called the extraintestinal pathogenic *E. coli* (ExPEC). Usually the ExPEC are also harmless colonizers but under certain circumstances can translocate and cause infection. The main virulence factor responsible for this translocation is the HlyA toxin, which pathogen is mainly associated with severe UTI but in addition with bacteremia and extraintestinal infections. In this chapter an exhaustive description of the toxin has been delineated; including its synthesis, maturation, and export from the bacteria. Effects produced by HlyA in different target organs have also been discussed. The significance of the maturation process for the toxin cannot be understated. The acylation of the protein at two internal lysines gives the toxin its virulence, by exposing intrinsic disordered regions that are essential to different steps of the toxin's mechanism of action. The further exposure of regions involved in the protein-protein interaction within the oligomerization process is responsible for the permeability induced in all the target cells, despite the intracellular signal pathway the toxin induces in each specific organ. This activation is unique to prokaryotic proteins.

Based on the already known structural and functional characteristics of HlyA, we might speculate about its use in toxin-based therapy. Such therapy is a versatile and dynamic research area with a great potential application. Further investigation, however, is required in order to improve the efficiency and safety of toxin-based agents. Investments in the development of delivery and targeting techniques are definitely needed in order to achieve this goal, though the basic research on the structure and mechanism of natural toxins should nevertheless not be abandoned. Topics related to HlyA have still to be clarified concerning the existence of a toxin-specific receptor in target cells and the domains of the toxin involved in its interaction with those putative binding sites. The deeper our knowledge becomes about this unique family of secreted polypeptides, the more easily will we be able to harness their great potential for our own benefit.
