Health. Antibiotic resistance: a new strategy to disarm bacteria while preserving the microbiota

According to the World Health Organization (WHO), antibiotic resistance is responsible for nearly 5 million deaths each year.

This resistance could become the leading cause of death by 2050. The cause: excessive or inappropriate use of antibiotics, which encourages the emergence of increasingly resistant bacteria.

Although antibiotics have significantly reduced deaths from infectious diseases, their broad and nonspecific action has harmful consequences: by destroying not only pathogenic bacteria but also those in the microbiota, they weaken the natural balance of our bodies. Finding innovative alternatives therefore appears to be a priority for public health.

Mfd, a major protein

A research team coordinated by the French National Institute for Agriculture, Food, and the Environment (INRAE) has identified a key target for fighting bacteria: the Mfd protein. This protein, common to many bacteria, plays a crucial role on two levels:

• it allows bacteria to resist the host's immune system;
• It promotes the appearance of random mutations, thus increasing their capacity to develop resistance.

By blocking this protein, it would therefore be possible to disarm bacteria while reducing their potential for mutation.

To neutralize the Mfd protein, the researchers tested more than 5 million molecules. Among them, the NM102 molecule proved particularly promising. The tests, conducted in the laboratory and on animal models (insects and mice), revealed three major effects:

• it does not kill bacteria directly, but prevents them from producing toxic compounds against the immune system;
• It reduces pathogenic bacteria in infected organs, while sparing the microbiota.
• It blocks the mutagenic function of the Mfd protein, thus limiting the appearance of new resistance.

A three-pronged approach that disarms bacteria instead of destroying them. This protects beneficial bacteria in the microbiota and remains effective against strains resistant to current antibiotics.

The team is now continuing its work to optimize NM102 and develop drugs capable of combating antibiotic resistance. It has already succeeded in encapsulating this molecule in biodegradable nanoparticles to facilitate its administration.