Strategy for more effective antibiotics- conjugation to a molecular transporter

Researchers at Stanford have developed a strategy to improve the efficacy of antibiotics by conjugating the antibiotic to a guanidinium-rich molecular transporter (GR-MoTr). The overuse of antibiotics has led to increasing development of antibiotic-resistant bacteria, including “superbugs”, with more than 2 million people infected in the U.S. per year. To further complicate matters, new antibiotic development has lagged. Thus, there is a major need for new therapeutics against bacterial infections, especially for those that can overcome antibiotic-resistance and eradicate chronic infections. To help meet this need, the inventors took advantage of their molecular transporter technology (see Stanford Docket S15-370). Here, they have conjugated the molecular transporter to the conventional antibiotic, vancomycin. The molecular transporter helps keep vancomycin associated with the cell enabling it to outperform conventional vancomycin. The conjugate is effective in eradicating vancomycin-resistant bacteria, slow-growing biofilms, stationary and persister cells, and is capable of reducing the intracellular bacterial load in infected mammalian skin cells. This technology provides the means to effectively treat multi-drug resistant and biofilm-associated bacteria linked to recurrent and chronic infections.

Stage of research
The inventors have shown that the vancomycin-GR-MoTr conjugate outperforms conventional vancomycin (often by orders of magnitude) in persister cell and biofilm assays, and demonstrates a faster bactericidal mode of action, tighter membrane association and intracellular accumulation. Further, the conjugate reduced biofilm loads in vivo, while exhibiting no acute toxicity or damage to skin cells.