Mechanism by which ‘superbugs’ neutralize antibiotics uncovered; Ewha Womans University finds clue to overcoming resistance

[Financial News] Korean researchers have identified, at the atomic level, how an enzyme in bacteria works to neutralize antibiotics and create powerful “superbugs.” They found that two water molecules inside the enzyme cooperate when bacteria destroy antibiotics, a discovery expected to mark a new turning point in developing next-generation treatments for antibiotic-resistant bacteria.
Ewha Womans University said on the 4th that a joint research team led by Professor Cha Seon-sin of the Department of Chemistry and Nanoscience and Professor Choi Seon of the College of Pharmacy had identified the key process and mechanism by which bacteria break down antibiotics and render them ineffective. The findings were published online on October 27 in the international journal ACS Catalysis.
Beta-lactam antibiotics such as penicillin and cephalosporins kill bacteria by breaking down their cell walls. However, some bacteria, including Gram-negative bacteria that cause pneumonia and sepsis, resist them by producing an enzyme called beta-lactamase, which destroys the antibiotics’ structure. It was already known that water molecules are involved in the process by which this enzyme eliminates antibiotics, but exactly which water molecules play what roles had not been clearly established.
The research team used synchrotron X-rays and a high-performance supercomputer to capture, at high resolution, the moment when cefotaxime, a third-generation cephalosporin antibiotic, binds to a resistance enzyme. Their analysis confirmed that another water molecule is present inside the enzyme in addition to the one already known.
The two water molecules divide up their roles as they act inside the enzyme. The first water molecule activates the second, which then directly attacks and destroys an antibiotic intermediate. The findings reveal a kind of “teamwork” mechanism through which bacteria precisely neutralize antibiotics.
With the precise pathway by which antibiotics are broken down now identified, it is expected to become easier to design next-generation antibiotics and treatments for resistance that can evade bacterial resistance mechanisms or inhibit the activity of this enzyme.
Professor Choi Seon of Ewha Womans University said, “This study precisely explains, at the atomic level, the key process by which antibiotic resistance enzymes neutralize drugs,” adding, “It will provide an important foundation for developing new drugs and devising strategies to overcome antibiotic resistance in the future.”

[email protected] Kim Man-gi Reporter