A New Type of Antibiotic That is not Afraid of Bacterial Infection

Scientists at the Wistar Institute have discovered a new type of compound that can quickly combine antibiotics that directly kill the proliferation of bacteria and protozoa with the immune response to combat antibiotic substitution (AMR). Therefore, the study was published recently in ” Nature.
Nature: A new type of antibiotic that is not afraid of bacterial infection is born!

The World Health Organization (WHO) announced that AMR has become one of the top ten public threats to humanity in the world. It is predicted that by 2050, drug-resistant infections may kill 10 million people every year and cause a burden of hundreds of billions of dollars on the global economy. The number of bacteria that are resistant to all available antibiotics is increasing, and there are few new drugs under development. Therefore, there is an urgent need for new antibiotics to prevent public health crises. , A two-pronged strategy to develop new molecules that can kill difficult-to-treat infections while enhancing the natural host’s immune response.

However, bacteria can be obtained by mutating the bacterial target gene targeted by antibiotics, inactivating the drug or pumping it out. Researchers believe that using the immune system to attack two different bacteria at the same time makes it difficult for them to develop resistance.
Fluorescence microscope staining shows the effect of DAIA treatment on bacterial viability

Researchers have been focusing on exploring metabolic pathways that are essential to most bacteria but do not exist in humans, making them ideal targets for the development of antibiotics. This is called methyl D-erythryl sugar alcohol phosphate (MEP) or non-methoxy valerate pathway, responsible for the biosynthesis of isoprenoids, which are the cells in most pathogenic bacteria Molecules needed for survival. The laboratory research focused on the IspH enzyme, which is essential for isoprene biosynthesis, with the goal of interrupting this pathway and killing microorganisms.
Researchers used computer modeling methods to screen out the ability of millions of compounds to bind to enzymes, and selected the most effective compound to inhibit IspH function as the starting point for drug development. Since the previously available IspH inhibitors cannot penetrate the bacterial cell wall, a number of senior scientists worked together to identify and synthesize a new IspH of inhibitor molecules that can enter the bacteria.
The team proved that in vitro testing of clinical isolates of a variety of selective bacteria including antibiotics, IspH inhibitors are more effective than current best-in-class antibiotics on the immune system. In preclinical models of gram-negative bacterial infections, the bactericidal effect of IspH inhibitors replaces traditional pan-antibiotics and shows that all tested compounds have no toxic effects on human cells.
We believe that this innovative DAIA strategy may represent the potential consequences of fighting AMR in the world, creating a synergy between the direct killing ability of antibiotics and the natural forces of the immune system.
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