Encapsulated Methionine γ-Lyase: Application in Enzyme Prodrug Therapy of Pseudomonas aeruginosa Infection

Abstract

Lung disease caused by Pseudomonas aeruginosa is the leading reason for death in cystic fibrosis patients. Therapeutic efficacy of the pharmacological pairs, the naked/encapsulated mutant form of Citrobacter freundii methionine γ-lyase and the substrates, sulfoxides of S-substituted l-cysteine, generating thiosulfinates, was evaluated on the murine model of experimental sepsis caused by the multidrug-resistant P. aeruginosa 203-2 strain. The pairs containing the naked enzyme and substrates did not have antibacterial activity. The treatment of mice with the pair encapsulated enzyme and S-methyl-l-cysteine sulfoxide, generating dimethyl thiosulfinate, led to a complete recovery of the animals of the model, with the infecting dose equal to LD50. The pair generating diallyl thiosulfinate (allicin) proved to be less effective. So, the substituents, attached to the thiosulfinate moiety, affect the antibacterial activity of thiosulfinates against P. aeruginosa.