ST1-YtnP lactonase from extreme environment: A promising antivirulence agent against multidrug-resistant Pseudomonas aeruginosa.

Abstract

The emergence of multidrug-resistant (MDR) pathogens, particularly Pseudomonas aeruginosa, requires innovative therapeutic strategies. This study investigates the potential of ST1-YtnP lactonase, an enzyme isolated from the thermophilic bacterium Bacillus licheniformis, which is found in the extreme environment of the Vranjska Banja hot springs. The extreme conditions in this habitat offer untapped potential for the discovery of biotechnologically valuable, resilient enzymes. ST1-YtnP lactonase was shown to effectively degrade acyl-homoserine lactones (AHLs), thereby disrupting the quorum sensing (QS) system of P. aeruginosa and reducing its virulence. ST1-YtnP significantly reduced biofilm formation without inhibiting bacterial growth Furthermore, in vitro analysis revealed that ST1-YtnP lactonase exhibited a synergistic effect with gentamicin and an additive effect with meropenem, enhancing the efficacy of these antibiotics against P. aeruginosa MMA83. In vivo, the combination of meropenem and ST1-YtnP lactonase completely rescued Caenorhabditis elegans from infection, surpassing the protective effect of meropenem alone. ST1-YtnP lactonase showed no adverse effects on the survival of uninfected nematodes, while it significantly enhanced the survival of P. aeruginosa-infected nematodes treated with the enzyme. These findings emphasize the potential of ST1-YtnP lactonase as a novel antivirulence agent with promising biotechnological applications to combat antibiotic-resistant infections.