Jun 09, 2024 20:00:00

Introducing the antibiotic 'Loramycin' that targets only pathogenic bacteria, a 'smart antibiotic' that destroys bad bacteria while protecting good bacteria

Taking antibiotics can kill beneficial bacteria in the intestines, so intestinal regulators are often prescribed along with antibiotics. A study on loramycin, an antibiotic that destroys only

gram-negative bacteria , which include many pathogenic bacteria such as E. coli and Salmonella, while leaving other harmless resident bacteria unaffected, was published in the scientific journal Nature.

A Gram-negative-selective antibiotic that spares the gut microbiome | Nature
https://www.nature.com/articles/s41586-024-07502-0

New Era? 'Double Selective' Antibiotic Spares the Microbiome
https://www.medscape.com/viewarticle/new-era-double-selective-antibiotic-spares-microbiome-2024a1000apx

'Smart' antibiotic can kill deadly bacteria while sparing the microbiome
https://www.nature.com/articles/d41586-024-01566-8

Gram-negative bacteria are considered a medical nightmare because they are hardy, toxic, and quickly acquire resistance to antibiotics. There are antibiotics, such as colistin , that target only gram-negative bacteria, but because there are also harmless and beneficial gram-negative bacteria among them, indiscriminately destroying gram-negative bacteria will also destroy the intestinal flora that prevents the proliferation of pathogenic bacteria.

One of the reasons why gram-negative bacteria are resistant to antibiotics is because of the double defense barrier of the outer and inner membranes. Therefore, a research team led by Kristen A. Muñoz of the University of Illinois at Urbana-Champaign developed an antibiotic called loramycin that takes advantage of the existence of this defense system.

Loramycin works by inhibiting the Lol system, which transports lipoproteins that are important in the production of membranes that protect gram-negative bacteria, while having almost no effect on gram-positive bacteria.

In addition, by taking advantage of the differences in the Lol systems of pathogenic and non-pathogenic gram-negative bacteria, the research team succeeded in developing an antibiotic that targets only the disease-causing gram-negative bacteria.

'Gram-positive bacteria don't have an outer membrane, so they don't have the Lol system,' says Muñoz. 'We also compared the Lol systems in pathogenic and beneficial gram-negative bacteria and found that they are very different.'

To verify the efficacy of loramycin, the research team used it on pathogenic Gram-negative bacteria cultured in the laboratory, and confirmed that it had an antibacterial effect against more than 130 strains of multidrug-resistant bacteria. In addition, in an experiment using mice infected with resistant bacteria, all mice administered loramycin survived, while 87% of the mice not administered loramycin died within three days.

Furthermore, mice administered common antibiotics had their intestinal flora destroyed and were infected with

Clostridioides difficile, which grows after antibiotic treatment and causes diarrhea, but mice administered loramycin did not become infected, indicating that loramycin protects the intestinal flora and prevents secondary infections.

Although loramycin has shown promising results in experiments on mice, it typically takes 10 to 20 years or more for a drug to be proven safe in human clinical trials and approved by drug authorities, so there is a long way to go before it can be used in practical applications.

'Although there is still a lot of work to be done in terms of evaluating loramycin's potential applications, we are optimistic about the future of this drug,' Munoz said.