Exotoxin A is essential in the pathogenesis of P. aeruginosa , it is a NAD-dependent ADP-ribosyltransferase that inactivates eukaryotic elongation factor 2 (eEF-2), resulting in the inhibition of protein synthesis and cell death (POLLACK, 1984). Given its importance in bacterial virulence, exotoxin A represents a promising therapeutic target for the development of new treatment strategies.
The analysis of specific inhibitors of exotoxin A may provide an alternative and complementary view to conventional antibiotics , potentially circumventing the mechanisms of antimicrobial resistance. Inhibitors are molecules that bind to a target enzyme or protein, in this case exotoxin A, interfering with its function. They can act in several ways, such as competing for the enzyme's active site, inducing conformational changes that prevent catalytic activity, or blocking the interaction of the toxin with its substrate. Exotoxin A inhibitors could, for example, prevent the binding of NAD+ or eEF-2, or interfere with the transfer of the ADP-ribosyl group, thus neutralizing the toxic activity of the protein . The inhibition process may be reversible or irreversible, depending on the nature of the interaction between the inhibitor and the toxin. Furthermore, selective inhibition of exotoxin A may reduce bacterial virulence without necessarily eliminating the pathogen, which could decrease the selective pressure for the development of resistance.
POLLACK, Matthew. The Virulence of Pseudomonas aeruginosa . Clinical Infectious Diseases , v. 6, n. Supplement_3, p. S617–S626, 1984. Available at: < https://academic.oup.com/cid/article-abstract/6/Supplement_3/S617/295939?login=false >. Accessed: August 7, 2024.
Comentarios