The original antibiotic compound lolamicin successfully treated bacterial infections in animal models without disrupting beneficial gut microbes. The University of Illinois team led by chemistry and biomedical sciences professor Paul Hergenrother continues to develop lolamicin derivatives. This drug class is unique for both sparing healthy microbiota and targeting pathogenic gram-negative bacteria among the toughest infections to treat. Hergenrother’s lab based their work on compounds initially explored by AstraZeneca which inhibit the Lol system a lipoprotein transport pathway found only in gram-negative bacteria.

Although the original compounds weren’t effective antibiotics we saw potential because the Lol system differed genetically between harmful and beneficial microbes said Professor Paul Hergenrother. His team created structural variants of the Lol inhibitors and tested their ability to kill both gram-negative and gram-positive bacteria in lab settings. Lolamicin selectively targeted gram-negative pathogens such as E. coli K. pneumoniae and E. cloacae while showing no activity against gram-positive bacteria.

At higher concentrations lolamicin successfully eliminated up to 100% of multidrug-resistant clinical isolates of the targeted gram-negative strains. In animal studies oral treatment with lolamicin cured 100% of mice with drug-resistant septicemia and 70% with pneumonia. Crucially it preserved the gut microbiome unlike conventional antibiotics that often disrupt beneficial bacteria. These findings were published in Nature in 2024.

Pathogenic strains like E. coli and K. pneumoniae are linked not only to septicemia and pneumonia but also to various inflammatory diseases and even certain cancers noted Professor Hergenrother. We hope these new antibiotics will become life-saving treatments for hard-to-treat infections and potentially other conditions as well he said.

Though promising the lolamicin drug class remains in the early stages of development. Further preclinical studies are needed to confirm safety and efficacy before submitting an Investigational New Drug (IND) application to the FDA. If successful human clinical trials could begin as early as 2026 according to Matt Tindall Executive Chairman and CEO of Flightpath Biosciences which holds the exclusive global license for the lolamicin platform. 

The novel mechanism of action behind these targeted drug candidates could be transformative for treating infection-driven diseases said Matt Tindall. They work by preserving the healthy microbiome and immune system rather than disrupting them. The lolamicin platform aligns perfectly with Flightpath’s mission to eliminate harmful pathogens while protecting the patient’s microbiome.

Source: https://medicine.illinois.edu/news/biotech-company-licenses-new-microbiome-sparing-antibiotic-developed-at-illinois