Antibiotic kills gram-negative bacteria, spares gut microbiome

Gut microbiome

Researchers have developed a new antibiotic that reduced or eliminated drug-resistant bacterial infections in mouse models of acute pneumonia and sepsis while sparing healthy microbes in the gut.

The drug, called lolamicin, also warded off secondary infections with Clostridioides difficile, and was effective against more than 130 multidrug-resistant bacterial strains in cell culture.

“People are starting to realise that the antibiotics we’ve all been taking – that are fighting infection and, in some instances, saving our lives – also are having these deleterious effects on us,” said Professor Paul Hergenrother, University of Illinois Urbana-Champaign Chemistry.

Numerous studies have found that antibiotic-related disturbances to the gut microbiome increase vulnerability to further infections and are associated with gastrointestinal, kidney, liver and other problems.

The few drugs available to fight gram-negative infections also kill other potentially beneficial gram-negative bacteria.

To tackle the many problems associated with indiscriminately targeting gram-negative bacteria, the team focused on a suite of drugs developed by AstraZeneca.

These drugs inhibit the Lol system, a lipoprotein-transport system that is exclusive to gram-negative bacteria and genetically different in pathogenic and beneficial microbes.

These drugs were not effective against gram-negative infections unless the researchers first undermined key bacterial defences in the laboratory.

Lolamicin had no detectable effect on gram-positive bacteria in cell culture. At higher doses, lolamicin killed up to 90% of multidrug-resistant E. coli, K. pneumoniae and E. cloacae clinical isolates.

When given orally to mice with drug-resistant septicemia or pneumonia, lolamicin rescued 100% of the mice with septicemia and 70% of the mice with pneumonia, the team reported.

The researchers caution that this is just a proof-of-concept study that antibiotics that kill a pathogenic microbe while sparing beneficial bacteria in the gut can be developed for gram-negative infections, but much more research is needed.

Diana Spencer, Senior Digital Content Editor, DDW

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