New antibiotics active against a wide range of bacteria

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In a new study, researchers found a new class of antibiotics that can actively fight against a wide range of bacteria.

The research was conducted by Wistar Institute scientists.

The World Health Organization (WHO) has declared AMR as one of the top 10 global public health threats against humanity.

It is estimated that by 2050, antibiotic-resistant infections could claim 10 million lives each year and impose a cumulative $100 trillion burden on the global economy.

The list of bacteria that are becoming resistant to treatment with all available antibiotic options is growing and few new drugs are in the pipeline, creating a pressing need for new classes of antibiotics to prevent public health crises.

In the study, the team took a creative, double-pronged strategy to develop new molecules that can kill difficult-to-treat infections while enhancing the natural host immune response.

They identified a new generation of antimicrobials named dual-acting immuno-antibiotics (DAIAs).

Existing antibiotics target essential bacterial functions, including nucleic acid and protein synthesis, the building of the cell membrane, and metabolic pathways.

However, bacteria can acquire drug resistance by mutating the bacterial target the antibiotic is directed against, inactivating the drugs or pumping them out.

The team focused on a metabolic pathway that is essential for most bacteria but absent in humans, making it an ideal target for antibiotic development.

This pathway is responsible for biosynthesis of isoprenoids — molecules required for cell survival in most pathogenic bacteria.

Researchers used computer modeling to screen several million commercially available compounds for their ability to bind with the enzyme, and selected the most potent ones that inhibited IspH function as starting points for drug discovery.

They believe this innovative DAIA strategy may represent a potential landmark in the world’s fight against antimicrobial resistance, creating a synergy between the direct killing ability of antibiotics and the natural power of the immune system.

One author of the study is Farokh Dotiwala, M.B.B.S., Ph.D., an assistant professor in the Vaccine & Immunotherapy Center.

The study is published in Nature.

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