Seeking a Simple Solution

The resistance of bacteria to antibiotics is a global challenge that has been exacerbated by the financial burdens of bringing new antibiotics to market and an increase in serious bacterial infections as a result of the COVID-19 pandemic.

Researchers in the lab of Kyle Allison, assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University are tackling the problem of antibiotic resistance not by creating new drugs, but by enhancing the safety and potency of ones that already exist.

Aminoglycosides are antibiotics used to treat serious infections caused by pathogenic bacteria like E. coli or Klebsiella.  Importantly, bacteria haven’t developed widespread resistance to aminoglycosides, as compared to other types of antibiotics.  These antibiotics are used sparingly by doctors, in part because of the toxic side effects they can sometimes cause.

In new research published recently in the journal PLOS One, authors Christopher Rosenberg, and Allison (who is also a researcher in the Petit Institute for Bioengineering and Bioscience at Georgia Tech) that lower doses of aminoglycosides could be used to treat bacteria when combine with specific metabolic sugars.  Low concentrations of antibiotics alone often cannot eliminate dormant, non-dividing bacterial cells, but the researchers hypothesized, based on a past study, that combining aminoglycosides with metabolites such as glucose, a simple sugar, or mannitol, a sugar alcohol often used as sweetener, could stimulate antibiotic uptake.

The authors tested these treatment combinations against Gram-negative pathogens E. coli, Salmonella and Klebsiella. The results showed that aminoglycoside-metabolite treatment significantly reduced the concentration of antibiotic needed to kill those pathogens.  Of note, the authors also demonstrated that this treatment combination did not increase bacterial resistance to aminoglycosides and was effective in treating antibiotic-tolerant biofilms, which are bacterial communities that act as reservoirs of infection.

Authors also found that one metabolite, mannitol, could reduce the kidney cell toxicity caused by aminoglycosides, independent of its effect on bacteria. This indicates that certain metabolites can exploit the metabolism of bacteria while also protecting human cells from toxicity.

The study suggests that there may be simple strategies to boost the safety and effectiveness of the drugs already available, and that this type of approach could be a useful alternative to developing new antibiotics.

Link to paper: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237948

Link to lab: https://sites.gatech.edu/kyle-allison-lab/

Writer: Quinn Eastman, Emory