Antimicrobial resistance: A new method to overcome the threat

Conformational changes in multidrug efflux adaptor proteins: Implications for inhibition.


Antimicrobial resistance (AMR) has emerged as a critical global health challenge, rendering many antibiotics and antimicrobial agents ineffective against bacterial infections. Researchers have made a significant breakthrough in pursuing innovative solutions to overcoming AMR. This pioneering study explores a novel method that could potentially restore the effectiveness of existing antimicrobial treatments and open new avenues in combating drug-resistant bacteria.

The University of Oklahoma‘s Center for Antibiotic Discovery and Resistance, led by Dr. Helen Zgurskaya and Dr. Valentin Rybenkov, seeks alternative therapeutic solutions to combat antimicrobial resistance (AMR). According to the World Health Organization, AMR has become a global threat, with most clinical antibiotics losing their effectiveness against certain pathogenic bacteria.

Bacteria can become antibiotic-resistant through various mechanisms, including developing efflux pumps, which pump antibiotics out of the cell before they can take effect. However, the OU researchers’ recent discovery, published in Nature Communications, involves a new class of molecules that inhibit the efflux pump, thereby making antibiotics effective once again in treating drug-resistant bacteria. This breakthrough offers promising prospects in the fight against AMR and the development of innovative treatments.

Helen Zgurskaya, a George Lynn cross-research professor, said, “We already live in a post-antibiotic era, and things will get much worse unless new solutions are found for antibiotic resistance in clinics. Our discoveries will facilitate the development of new treatments to help mitigate an impending crisis.”

In collaboration with teams from the Georgia Institute of Technology and King’s College London, researchers at the University of Oklahoma’s Center for Antibiotic Discovery and Resistance have made a significant breakthrough in understanding the mechanism of action of novel inhibitors. These inhibitors function as “molecular wedges” that target the region between the inner and outer cell membranes of bacteria, enhancing the effectiveness of antibiotics. This discovery holds promise for developing new therapeutics to combat antimicrobial resistance and improve clinical applications of antibiotics.

The discovery of this novel method to overcome antimicrobial resistance is a significant advancement in the fight against drug-resistant bacteria. By targeting specific genes and resistance mechanisms and using compounds to enhance the efficacy of existing antimicrobials, this approach offers new hope in addressing the global challenge of AMR.

If successfully translated into clinical practice, this breakthrough can revolutionize treatment strategies, preserve the efficacy of current antimicrobials, and improve patient outcomes in the face of antimicrobial resistance.

Journal Reference:

  1. Russell Lewis, B., Uddin, M.R., Moniruzzaman, M. et al. Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein. Nature Communication.DOI:10.1038/s41467-023-39615-x
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