Bacteria-Targeting Conjugates Based on Antimicrobial Peptide for Bacteria Diagnosis and Therapy.

Chloramphenicol (CAP) is one of the most effective antimicrobial agents, but its therapeutic efficacy is greatly limited by its nonspecific distribution and consequent side effects in neutrophils. Targeting to the infection sites, and thus restricting CAP nonselective delivery, provides an alternative way to overcome this limitation. The antibacterial peptide fragment UBI29-41 was identified to have a high bacterial affinity. However, no research so far has been carried out to utilize UBI29-41 as a ligand for bacteria-targeting therapies. In this Article, we first labeled a near-infrared fluorescent dye (ICG02) with UBI29-41 to investigate its targeting capability in different bacteria (S. aureus, E. coli, and P. auruginosa) and bacteria-infected mouse models. Subsequently, UBI29-41 was conjugated with the typical antibiotic (CAP) through the linker glutaric anhydride to form the conjugate CAP-UBI29-41 for the bacteria-targeting therapy. In vitro studies demonstrated the enhanced antibacterial effects of CAP-UBI29-41 on S. aureus and E.coil. Meanwhile, the toxicity of CAP-UBI29-41 on normal cells decreased distinctly in comparison with CAP. Most importantly, CAP-UBI29-41 exhibited more favorable antibacterial efficacy than CAP in bacteria-bearing mouse models. All these results demonstrated that UBI29-41 is an ideal targeting ligand to construct antibacterial agents for bacteria-targeting therapy.