Solution

We employ a two-pronged approach to address antibiotic resistance, with nature-inspired chemistry at the core. 

Our approach will address antibiotic resistance in two ways: by applying our technology to develop structurally-unique resistance modifying agents (RMAs) and by producing first-in-class, broad spectrum antimicrobials. Each program offers unique advantages and a path forward in the fight against antibiotic resistance. 

β-lactams revolutionized modern medicine, their widespread use saved millions of lives over the past century from the ravages of bacterial infections.(1) Unfortunately, infectious bacteria were able to adapt and become resistant to the β-lactams disabling their utility in the clinic. We have developed a set of compounds from our core structure that will reverse bacterial resistance to β-lactam antibiotics. When paired with our RMAs, β-lactams regain their potency against MRSA. The RMA technology will allow the extremely safe β-lactam, previously effective antibiotics to realize clinical use once again. 

Infectious bacteria can be divided into two major classes: Gram-positive and Gram-negative.(2) Unlike Gram-positive bacteria, whose cells are surrounded by a single membrane, the Gram-negative bacteria are surrounded by two membranes which block out many otherwise effective antibiotics.(3) Such Gram-negative pathogens are becoming particularly concerning as carriers of antibiotic resistance since their outer membrane confers a daunting hurdle for new drug discovery.(4) Through extensive chemical modification of our scaffolds, we have discovered an approach to produce compounds that possess potent antibacterial activity against even the most difficult Gram-negative bacteria as well as Gram-positive bacteria. These will be developed as novel first-in-class broad-spectrum antibiotics.

Our chemical scaffolds are completely synthetic in origin, but they were designed based on the indole-alkaloids, a bioactive class of compounds occurring naturally in plants and other organisms. Our natural-product inspired technologies are each first-in-class forms of antibiotic treatment and offer new and exciting solutions to address the antibiotic resistance crisis. 

1. Kardos, N.; Demain, A. L. Penicillin: The Medicine with the Greatest Impact on Therapeutic Outcomes. Appl. Microbiol. Biotechnol. 2011, 92 (4), 677–687.
2. Wilson, B. A.; Salyers, A. A.; Whitt, D. D.; Winkler, M. E. Bacterial Pathogenesis; American Society of Microbiology, 2011.
3. Hancock, R. The Bacterial Outer Membrane as a Drug Barrier. Trends Microbiol. 1997, 5 (1), 37–42.
4. Nikaido, H. Molecular Basis of Bacterial Outer Membrane Permeability Revisited. Microbiol. Mol. Biol. Rev. 2003, 67 (4), 593–656