The continual rise of antibiotic resistance – coupled with the shrinking pipeline of new antibiotics – poses a major threat to global health. The traditional approach to solve this growing problem typically relies on developing structural analogs of existing antibiotics, pursuing new leads, or even revisiting previous compounds that were at one point considered very toxic. Combination therapy that combines multiple small-molecule antibiotics into one treatment is also a common strategy to overcome resistance in bacteria, however, it can also be quite toxic. In recent years, these approaches have not only been outpaced by the onset of resistance, but the situation is exacerbated by the fact that the number one reason most antibiotics fail is due to a lack of solubility in water and their inability to permeate bacterial cell membranes. In my presentation, I will describe a different strategy that my laboratory is currently investigating; one which involves precise supramolecular receptors built into a polymer platform, where each receptor can be loaded with different combinations of antimicrobial agents, depending on the type of multidrug-resistant bacteria that is to be treated. Moreover, this platform is easily converted into larger nano-based structures, which stabilize the loaded drugs and allows for selective targeting of bacteria through specific cell surface-based interactions. Since no pro-drugs are involved, the mechanism of action of each agent is unperturbed and each undergoes slow release in a predictable manner. Lastly, I will discuss <i>in vivo </i>efficacy studies against different drug-resistant bacterial strains, and how our next-generation platform is an ideal material for sustained protection that may prove useful in wound healing applications, among others.

Supramacromolecular strategy to combat multidrug-resistant bacteria

255th National Meeting (2018)

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