Scientists from the University of Oklahoma’s Center for Antibiotic Discovery and Resistance have isolated molecules capable of impeding bacterial efflux pumps, thereby bolstering the effectiveness of antibiotics. This innovative development, grounded in a “molecular wedge” methodology, presents a viable pathway for pioneering therapies aimed at combatting antibiotic resistance.
The World Health Organization has categorized antimicrobial resistance as a global issue, given the reduced efficacy of most contemporary clinical antibiotics against specific disease-causing bacteria. The Center for Antibiotic Discovery and Resistance at the University of Oklahoma is spearheaded by Dr. Helen Zgurskaya and Dr. Valentin Rybenkov, both of whom are committed to researching alternative therapeutic interventions.
Antibiotics function by interacting with distinct components of bacterial cells, such as the cell wall or DNA. Bacterial cells can gain resistance to antibiotics through various mechanisms, including the evolution of efflux pumps—proteins situated on the cell surface. These pumps expel antibiotics from the cell before they can interact with their intended targets, rendering the antibiotics ineffective.
Recent findings by researchers from the University of Oklahoma, however, have been documented in the academic journal Nature Communications. The study introduces a new category of molecules that obstruct the efflux pump, thereby restoring the antibiotic’s potency.
These pump inhibitors employ an innovative action mechanism, which was previously not well-understood. The team led by Dr. Zgurskaya, in collaboration with researchers from the Georgia Institute of Technology and King’s College London, has ascertained that these inhibitors function as a “molecular wedge.” This wedge specifically targets the interface between the inner and outer bacterial cell membranes, amplifying the antibiotics’ antibacterial activities. This newfound understanding could expedite the development of next-generation therapeutics for clinical use.
Dr. Zgurskaya has noted, “We are already in a post-antibiotic epoch, and the situation will exacerbate if fresh approaches are not identified to tackle antibiotic resistance in clinical settings. Our contributions in this field will aid the creation of new therapies, thereby potentially averting a looming crisis.”
Reference: “Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein” authored by Benjamin Russell Lewis, Muhammad R. Uddin, Mohammad Moniruzzaman, Katie M. Kuo, Anna J. Higgins, Laila M. N. Shah, Frank Sobott, Jerry M. Parks, Dietmar Hammerschmid, James C. Gumbart, Helen I. Zgurskaya and Eamonn Reading, dated 18 July 2023, published in Nature Communications.
Dr. Helen Zgurskaya serves as the George Lynn Cross Research Professor, and Dr. Valentin Rybenkov is a Professor of Biochemistry. Both are affiliated with the Department of Chemistry and Biochemistry in the Dodge Family College of Arts and Sciences at the University of Oklahoma. Further information about their work at the Center for Antibiotic Discovery and Resistance can be obtained from relevant sources.
Frequently Asked Questions (FAQs) about Antimicrobial Resistance
What is the main discovery made by the researchers at the University of Oklahoma’s Center for Antibiotic Discovery and Resistance?
The primary discovery is the identification of molecules that inhibit bacterial efflux pumps. These pumps are responsible for expelling antibiotics out of bacterial cells, making them ineffective. By inhibiting these pumps, the effectiveness of antibiotics is restored.
What does the “molecular wedge” mechanism refer to?
The “molecular wedge” mechanism refers to the novel way these inhibitory molecules work. They target the area between the inner and outer bacterial cell membranes and act as a wedge that prevents the efflux pump from expelling antibiotics, thereby enhancing their antibacterial activities.
Who are the key people involved in this research?
The research is led by Dr. Helen Zgurskaya and Dr. Valentin Rybenkov, both of whom are part of the University of Oklahoma’s Department of Chemistry and Biochemistry. The team also collaborated with scientists from the Georgia Institute of Technology and King’s College London.
How does this discovery potentially impact the global issue of antimicrobial resistance?
The discovery opens a new avenue for developing alternative therapeutic solutions to tackle the global challenge of antimicrobial resistance. As most clinical antibiotics have lost their efficacy against certain bacteria, this research provides a promising route for creating more effective treatments.
Where was this research published?
This research was published in the academic journal Nature Communications, with the paper titled “Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein,” dated 18 July 2023.
What does Dr. Helen Zgurskaya say about the current state of antibiotic resistance?
Dr. Zgurskaya notes that we are already in a “post-antibiotic era” and warns that the situation will worsen unless new solutions are found to address antibiotic resistance in clinical settings. The research is aimed at facilitating the development of such new treatments.
How do antibiotics normally work and why do they become ineffective?
Antibiotics generally target specific components of bacterial cells, such as the cell wall or DNA, to kill or inhibit the bacteria. They become ineffective primarily because bacteria develop mechanisms like efflux pumps that remove the antibiotics from the cells before they can reach their targets.
More about Antimicrobial Resistance
- World Health Organization on Antimicrobial Resistance
- Nature Communications Journal
- University of Oklahoma’s Center for Antibiotic Discovery and Resistance
- Georgia Institute of Technology Research
- King’s College London Research
- Department of Chemistry and Biochemistry, University of Oklahoma
- DOI Reference for the Published Paper