Lectin-Targeted Prodrugs Activated by Pseudomonas aeruginosa for Self-Destructive Antibiotic Release

Area of Science:

• Microbiology
• Drug Discovery
• Bioconjugation

Background:

• Chronic *Pseudomonas aeruginosa* infections involve biofilm formation, contributing to antibiotic resistance.
• Fluoroquinolones are effective but associated with severe side effects.
• Bacterial lectins LecA and LecB are key biofilm components and potential drug targets.

Purpose of the Study:

• To develop novel lectin-targeted antibiotic prodrugs for *P. aeruginosa* infections.
• To investigate the targeted delivery and controlled release of fluoroquinolones.
• To evaluate the efficacy and safety profile of these prodrugs.

Main Methods:

• Conjugation of fluoroquinolones to lectin probes via cleavable peptide linkers.
• In vitro assessment of prodrug stability in plasma and liver metabolism.
• Evaluation of antibiotic release in the presence of *P. aeruginosa*.
• In vitro ADME and toxicity studies.

Main Results:

• Synthesized prodrugs demonstrated stability in host plasma and liver metabolism.
• Rapid and self-destructive release of antibiotic cargo upon encountering *P. aeruginosa* in vitro.
• Prodrugs exhibited favorable ADME properties and reduced in vitro toxicity.

Conclusions:

• Established the first lectin-targeted antibiotic prodrugs against *P. aeruginosa*.
• Demonstrated targeted delivery and controlled release mechanism for enhanced efficacy.
• Showcased potential for reduced systemic toxicity in treating chronic *P. aeruginosa* infections.