New antibiotic kills harmful bacteria, spares healthy gut microbes

Researchers have developed a new antibiotic drug that kills pathogenic bacteria while sparing healthy microbes.

Called lolamicin, the drug reduced or eliminated bacterial infections in mouse models of acute pneumonia. Crucially, it spared healthy microbes in the mouse gut.

According to researchers, the drug also warded off secondary infections with Clostridioides difficile, a common and dangerous hospital-associated bacterial infection, and was effective against more than 130 multidrug-resistant bacterial strains in cell cultures.

Next generation of antibiotics

“People are starting to realize 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 University of Illinois Urbana-Champaign chemistry professor Paul Hergenrother, who led the study with former doctoral student Kristen Muñoz.

“They’re killing our good bacteria as they treat the infection. We wanted to start thinking about the next generation of antibiotics that could be developed to kill the pathogenic bacteria and not the beneficial ones.” 

Antibiotic drugs can harm healthy gut microbes

Previous studies have revealed that antibiotic drugs create disturbances to the gut microbiome and make people vulnerable to further infections. Such drugs are also linked to gastrointestinal, kidney, liver and other issues. 

“Most clinically approved antibiotics only kill gram-positive bacteria or kill both gram-positive and gram-negative bacteria,” Muñoz said. 

He maintained that gram-positive and gram-negative bacteria differ in the composition of their cell walls.

“Gram-negative bacteria have a double layer of protection, making them more difficult to kill.”

Researchers claimed that the few drugs that fight gram-negative infections also eliminate beneficial gram-negative bacteria. Hence, they focused on a suite of drugs developed by the pharmaceutical company AstraZeneca to develop an antibiotic that doesn’t harm healthy gut microbes.

According to Hergenrother, 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 defenses in the laboratory.

Lolamicin rescued 100% of the mice with septicemia

However, because these antibiotics appeared to discriminate between beneficial and pathogenic gram-negative bacteria in cell culture experiments, they were promising candidates for further exploration.

“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,” reported the study published in Nature.

“The mouse microbiome is a good tool for modeling human infections because human and mouse gut microbiomes are very similar. Studies have shown that antibiotics that cause gut dysbiosis in mice have a similar effect in humans,” said Muñoz.

The team found that treatment with standard antibiotics amoxicillin and clindamycin caused dramatic shifts in the overall structure of bacterial populations in the mouse gut, diminishing the abundance several beneficial microbial groups.

“In contrast, lolamicin did not cause any drastic changes in taxonomic composition over the course of the three-day treatment or the following 28-day recovery,” concluded researchers.