New AstraZeneca-based antibiotic effectively kills harmful bacteria, spares beneficial ones

Researchers have identified a promising new antibiotic named lolamicin, which has the potential to treat severe bacterial infections such as sepsis and pneumonia without disrupting beneficial gut microbes. This discovery could address one of the major drawbacks of existing antibiotics, which often harm healthy gut bacteria and lead to serious complications.

The study, conducted by scientists from the University of Illinois Urbana-Champaign and published in Nature on May 29, describes how lolamicin was developed and tested. The drug originated from compounds initially discovered by AstraZeneca, although the pharmaceutical company was not directly involved in this research. Lolamicin targets the Lol system, a mechanism specific to gram-negative bacteria, which is essential for transporting lipoproteins within the bacterial cell.

Initial tests showed that lolamicin was particularly effective in killing harmful strains of gram-negative bacteria without affecting beneficial gram-negative strains found in the human gut. This selectivity makes it a strong candidate for developing new antibiotics that can combat challenging gram-negative pathogens without adverse effects on the microbiome.

Further modifications and tests revealed that high doses of lolamicin could kill up to 90% of various dangerous bacterial strains, including E. coli, Klebsiella pneumoniae, and Enterobacter cloacae, extracted from patient samples. Importantly, the drug showed no impact on gram-positive bacteria or beneficial gram-negative bacteria residing in the gut. Moreover, it was non-toxic to mammalian cell lines and red blood cells.

Animal studies provided more encouraging results. In mouse models of sepsis and pneumonia caused by multidrug-resistant strains of E. coli, K. pneumoniae, or E. cloacae, lolamicin treatment led to the survival of all sepsis-affected mice and 70% of those with pneumonia. In contrast, most mice treated with a control solution or a comparison drug died within 48 hours.

The researchers also examined lolamicin's effect on the gut microbiome in mice. They treated the animals with lolamicin, amoxicillin, or clindamycin for three days and then analyzed fecal samples over a month. While amoxicillin and clindamycin significantly reduced the proportion of beneficial gut microbes, lolamicin had minimal impact on the gut's bacterial ecosystem.

Furthermore, the team investigated whether lolamicin would influence the body's ability to clear Clostridioides difficile, a harmful microbe that can thrive after certain antibiotic treatments and cause secondary infections. The results showed that mice treated with lolamicin had very little C. difficile growth, unlike those treated with amoxicillin or clindamycin, which had high levels of C. difficile colonization.

Despite these promising findings, the researchers caution that it will take years before lolamicin or similar drugs are available for clinical use. There are still challenges to overcome, including reducing the risk of bacterial resistance to lolamicin and the broader issue of limited financial incentives for pharmaceutical companies to develop new antibiotics.

Nevertheless, the minimal disruption of the gut microbiome by lolamicin is seen as a significant advantage. The researchers believe that lolamicin could also be effective against other multidrug-resistant pathogens like Pseudomonas aeruginosa and Acinetobacter baumannii, which are common in hospital settings.

In conclusion, pathogen-specific antibiotics like lolamicin represent a promising approach to minimizing collateral damage to the gut microbiome, making them potentially superior to many existing antibiotics. This microbiome-sparing effect could lead to better outcomes for patients, particularly those suffering from severe infections caused by gram-negative bacteria.