The rise of multidrug antibiotic resistance has become a prevalent issue with over 2.8 million infections per year in the US alone. Conversely, there has been a steady decline in the production of new antibiotics that can overcome this resistance in recent decades. Therefore, there is a dire need to develop new methods to combat antibiotic resistant infections. Gram-negative bacteria in particular, such as <i>Pseudomonas aeruginosa</i> (PA), and <i>Escherichia coli </i>(EC), display an increased resistance to existing antibiotics due to their additional outer membrane (OM) preventing antibiotics from entering the cell. One way to overcome this resistance is through use of adjuvants capable of permeating the OM. This work evaluates the use of rationally designed, cleavable adjuvant/antibiotic hybrids to improve antibiotic activity against EC and PA compared to the traditional co-dosing adjuvant method.

Synthesis and evaluation of antibiotic/adjuvant hybrids capable of crossing the outer membrane of gram-negative bacteria

ACS Spring 2022

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