Cationic Constructs Overcoming Antibiotic Resistance

Invention Summary:

The spread of antibiotic resistance among bacterial pathogens in both hospital and community settings is occurring at an alarming rate, particularly to multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria. These “superbugs” resistant to multiple or to all antibiotic classes represent a serious threat to public health and require immediate public attention to prevent a global health crisis. Therefore, there is an urgent need for new paradigms in antibacterial drug development.

This invention disclosed two novel cationic constructs that are capable of binding to a bacterial cell and delivering an antibacterial agent to a bacterium at a surprisingly high concentration. The first construct (picture above) has a “spider-like” structure. Once bound, the anti-microbial drug load attached to the end of the spider’s arms via click chemistry inserts into the membrane or cytosol. This “cell poisoning” approach will deliver a high concentration of anti-microbial drugs to enhance their potency and efficacy. The second construct also shares a similar “spider-like” structure with a poly-lysine body and PEG arms.

However, in lieu of a drug-holding “hand”, two species of molecules that have affinity to bacteria and can form strong covalent bonds with each other based upon click chemistry are used as “hands.” Thus, when these macromolecules attach to the bacteria cell at a high density, a continuous web will cover the whole cell and trap it. This “cell entrapment” approach will impart their anti-microbial effect by preventing cell growth and proliferation. The inventor has demonstrated the click reaction between the cationic constructs on the bacterial cell surface in this approach.

The inventor has characterized both cationic constructs in terms of binding affinity to bacteria strains, drug release rate, and click chemistry reaction rate. It has been demonstrated that the constructs don't bind to mammalian cells, but have high affinity to major bacterial pathogens. The growth inhibitory activity of the synthesized constructs was also demonstrated in vitro.

Intellectual Property & Development Status:

Patent pending. Available for licensing or collaboration.

Rutgers ID: S2016-078
Life Sciences
Yong Zhang
Licensing Manager
Arkady Mustaev