Study Reveals Mechanics Behind How Penicillin Kills MRSA

A study published in the Proceedings of the National Academy of Sciences reveals the mechanism that allows beta-lactam antibiotics—which includes penicillin—to kill Methicillin-resistant S. aureus (MRSA) for the first time. It was previously known that beta-lactam antibiotics function by restricting cell wall growth, but the exact mechanics have remained unknown until now.

According to the investigators, beta-lactam antibiotics create holes in the cell wall, which enlarge as the cell grows, eventually killing the bacteria. The growth of these holes causes the cell wall to fail and results in death of the bacteria, which investigators now plan to use to create new therapeutics for antibiotic resistant superbugs.

“Penicillin and other antibiotics in its class have been a centerpiece of human healthcare for over 80 years and have saved over 200 million lives,” said Simon Foster, PhD, in a press release. “However, their use is severely threatened by the global spread of antimicrobial resistance. Concentrating on the superbug MRSA, our research revealed that the antibiotics lead to the formation of small holes that span the cell wall that gradually enlarge as part of growth-associated processes, eventually killing the bacteria. We also identified some of the enzymes that are involved in making the holes.”

The investigators were able to use this new knowledge and understanding of how the enzymes are controlled to demonstrate the efficacy of a novel combination therapy against MRSA. Using a simple model for bacterial cell wall expansion, they established a hypothesis for what happens when this is inhibited by antibiotics such as penicillin. These predictions were then tested using a combination of molecular approaches, including high resolution atomic force microscopy.

“Our findings get to the heart of understanding how existing antibiotics work and give us new avenues for further treatment developments in the face of the global pandemic of antimicrobial resistance,” Foster said in the release.


Scientists make breakthrough in understanding how penicillin works [news release]. EurekAlert; October 25, 2021. Accessed October 26, 2021.