Unveiling the Potential of the New Antibiotics Against Bacteria

A novel family of antibiotics with strong action against bacteria resistant to many drugs has been found by Uppsala University researchers, and they have demonstrated that this class of antibiotics may treat bloodstream infections in mice. The study was published in the journal PNAS.

Modern medicine is based on antibiotics, which have significantly improved people's lives worldwide during the past century. Antibiotics are a common medical tool that is often taken for granted. They are used extensively to treat or prevent bacterial infections, such as those that arise after cancer treatment, invasive surgery, transplants, and in pregnant women and their premature infants. 

However, the worldwide increase in antibiotic resistance is posing a growing danger to their efficacy. The development of new treatments against which there is no resistance is crucial to ensuring future access to effective antibiotics. 

Uppsala University researchers have described a novel class of antibiotics created as a result of multinational consortiums in the Proceedings of the National Academy of Sciences of the USA. The family of chemicals they describe targets a protein called LpxH, which Gram-negative bacteria employ in a pathway to synthesize lipopolysaccharide, their outermost layer of defense against the environment. 

While not all bacteria produce this layer, those that do include the ones that the World Health Organization has designated as the most important to treat with novel treatments: Escherichia coli and Klebsiella pneumoniae, which have already become resistant to the antibiotics that are currently on the market. 

The promise of this new class of antibiotics was demonstrated by the researchers, who were able to treat bloodstream infections in a mouse model and demonstrate the class's high level of activity against multidrug-resistant bacteria. Crucially, there is no pre-existing resistance to this class of chemicals because it is entirely novel and the protein LpxH has not yet been used as an antibiotic target. 

This stands in contrast to the several “me-too” antibiotics from the current class that are being developed for use in medicine. Even though the current results are extremely encouraging, a significant amount of more work must be done before drugs in this class are prepared for clinical trials. 

The Innovative Medicines Initiative's novel Drugs 4 Bad Bugs initiative (ND4BB) provided funding for the EU project ENABLE, which helped discover and develop this novel family of antibiotics. 

Under the direction of GlaxoSmithKline and Uppsala University researchers, the ENABLE project brought together academic institutions and small and large pharmaceutical companies from all over Europe to pool resources and expertise to advance the development of early-stage antibiotics. 

To maintain the momentum created by the first ENABLE project, this antibiotic class is currently being developed in the follow-up project, ENABLE-2, an antibiotic drug discovery platform funded by the Swedish Research Council, the National Research Programme on Antibiotic Resistance, and Sweden's innovation agency Vinnova.