Research studies reveal core principles of low-resistant antibiotics

Research published in Nature Communications reveals new insights into bacterial resistance and provides promising strategies for developing antibiotics that minimize the evolution of resistance.

Csaba Pal, D.Sc. At the Hun-Ren Biological Research Center in Hungary, the researchers demonstrated that a dual-target approach, combining membrane disruption and additional important cellular pathways, significantly prevents the development of bacterial resistance.

“Antibiotic resistance remains an important global challenge. Even antibiotics currently under development are beginning to encounter resistance as demonstrated in two recent publications. This underscores the urgent need to understand the underlying principles governing the effectiveness of antibiotics, reducing this escalating threat,” Csaba Pal, D.Sc.

Antibiotic resistance (AMR) is increasingly recognized as a silent pandemic, along with a projection that estimates up to 10 million deaths per year by 2050.

A rational dual target strategy

Called “dual target permeators,” this dual targeting approach shows the lowest level of resistance to important pathogens, such as E. coli, pneumoniasis, Acinetobacter Baumanni, Acinetobacter Baumanni, and Acinetobacter Baumanni, Acinetobacter Baumanni, and Acinetobacter Baumanni, which are identified by the World Health Organization (WHE).

Lead author Elvin Mahalamov said, “Combining membrane disruption with another important cellular pathway can dramatically limit bacterial resistance, which underscores the extent to which a particular target is important.”

Laboratory and environmental evidence

In laboratory evolution experiments, double target permeable agents produced consistently and consistent resistance levels compared to antibiotics targeting only bacterial membranes. The group includes the last resort polymyxin antibiotic and the yet-to-be-published derivative SPR206. Other dual-target antibiotics lacking membrane permeabilization showed median resistance levels up to 128-fold.

Furthermore, environmental samples important for understanding real-world applications revealed significantly fewer resistance genes associated with dual target permeators. In particular, no resistance determinants were detected for Tridecaptin M152-P3, but even antibiotics that have not yet been released for public use already show traces of resistance, highlighting the urgent need for improved drug design.

Future framework

“Antibiotics that penetrate the outer membrane of bacteria by targeting lipopolysaccharides (LPS) have been used for a long time in clinics. However, bacteria can rapidly evolve resistance to them, even the last-resorted antibiotics like Colistin.

This innovative mechanism of action may open up ways to develop next-generation antibiotics that are effective against multidrug-resistant Gram-negative pathogens.

By demonstrating that a rational dual-target approach can significantly reduce the risk of resistance, this study offers an important new direction in the fight against AMR. This research not only advances understanding of bacterial resistance mechanisms, but also lays the foundation for developing safer and more effective antibiotics to protect public health around the world.