This is how penicillin works on the cell wall of a resistant superbug

An investigation, led by the Sheffield University (United Kingdom), reveals that β-lactam antibiotics they kill the Staphylococcus aureus resistant to methicillin (MRSA), creating holes in its cell wall. Their growth leads to cell wall collapse and bacterial death. The finding is published today in the magazine Proceedings of the National Academy of Sciences (PNAS)

O methicillin is a type of penicillin – beta-lactam antibiotic – effective in treating infections caused by Staphylococcus aureus, a bacterium that inhabits the mucous membranes and skin of humans and causes a wide range of diseases.

“Penicillin and other antibiotics of this type have been a central element of human health for over 80 years and have saved more than 200 million lives. However, its use is seriously threatened by the worldwide spread of antimicrobial resistance“, Explain Simon Foster, Professor of Molecular Microbiology at the British University.

These drugs form holes in the MRSA cell wall, which enlarge and ultimately kill the bacteria.

Until now, it was known that β-lactam antibiotics acted by preventing cell wall growth, but exactly how they caused the bacteria to die was a mystery.

New therapies against antimicrobial resistance

According to the authors, these drugs cause the formation of small holes in the MRSA cell wall, which gradually increase as part of the processes associated with growth, leading to the bacteria’s death. Scientists have also identified some of the enzymes involved in the formation of these holes.

Now they intend to take advantage of this knowledge to create new therapies against superbugs resistant to antibiotics. “This discovery helps us understand how existing antibiotics work and facilitates the development of new treatments to deal with the global pandemic of antimicrobial resistance,” he said.

Thanks to greater knowledge and understanding of how enzymes work, the authors have also demonstrated the effectiveness of a new combination therapy against S. aureus.

To conduct this study, the team worked with a simple model of how the bacterial cell wall expands during growth and division, and hypothesized what happens when this is inhibited by antibiotics like penicillin. The predictions of this model were tested using a combination of molecular approaches, including the high resolution atomic force microscopy.

In addition to the University of Sheffield, the work involved groups from Xiamen University (China), Masaryk University (Czech Republic) and McMaster University (Canada).

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