The original antibiotic lolamicin successfully treated bacterial infections in animal models without disrupting beneficial gut microbes. The Illinois research team continues to develop its derivatives.

According to U. of I. chemistry professor Paul Hergenrother whose lab developed lolamicin this drug class stands out for both preserving healthy microbiota and targeting pathogenic gram-negative bacteria among the most challenging infections to treat.

Hergenrother’s team began their antibiotic development by examining a group of compounds previously studied by AstraZeneca which were known to inhibit the Lol system a lipoprotein transport mechanism found only in gram-negative bacteria.

While these initial compounds weren’t effective on their own we saw potential because the Lol system differs genetically between harmful and beneficial microbes Hergenrother explained.

Through a series of experiments the team created structural variants of the Lol inhibitors and tested their ability to kill both gram-negative and gram-positive bacteria in cell cultures. The results showed that lolamicin specifically targeted gram-negative pathogens such as Escherichia coli Klebsiella pneumoniae and Enterobacter cloacae while leaving gram-positive bacteria unaffected. At higher concentrations lolamicin successfully eliminated up to 100% of multidrug-resistant clinical isolates of these gram-negative strains.

Further testing showed that lolamicin was highly effective in animal models. When administered orally it cured 100% of mice with drug-resistant septicemia and 70% with pneumonia. Unlike standard antibiotics lolamicin did not disrupt the gut microbiome preserving beneficial bacteria. These findings were published in Nature in 2024. Hergenrother noted that since E. coli and K. pneumoniae are linked to various infections and even some cancers these antibiotics could have broader therapeutic potential.

The lolamicin drug class is still in the early stages of development with further preclinical studies needed to confirm the lead candidate’s safety and effectiveness. This will be followed by submission of 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 all applications of the lolamicin platform.

With its novel mechanism and targeted action lolamicin represents a potential breakthrough in treating infection-related diseases while preserving the healthy microbiome and immune system Tindall said. It aligns perfectly with Flightpath’s mission to eliminate harmful pathogens without compromising the patient’s microbiome.

Source: https://news.illinois.edu/flightpath-biosciences-licenses-microbiome-sparing-antibiotic-developed-at-illinois/