London: An international team of researchers has discovered how penicillin and other antibiotics kill MRSA (Methicillin Resistant S. aureus) superbug that is resistant to several antibiotics.

The team led by University of Sheffield, UK, along with Xiamen University in China, Masaryk University in the Czech Republic and McMaster University in Canada, found 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.

It was previously known that beta-lactam antibiotics work by preventing cell wall growth, but exactly how they kill has remained a mystery until now.

The team has also identified some of the enzymes that are involved in making the holes.

"Penicillin and other antibiotics in its class have been a centrepiece of human healthcare for over 80 years and have saved over 200 million lives. However, their use is severely threatened by the global spread of antimicrobial resistance," said Professor Simon Foster, from the University of Sheffield's School of Biosciences.

"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 added.

In the study, published in the journal Proceedings of the National Academy of Sciences, the scientists also showed the efficacy of a novel combination therapy against S. aureus.

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

Penicillin was discovered in London in September of 1928. In 1930 the first documented use of penicillin as a therapy was carried out in Sheffield by Cecil George Paine, a member of the University's Pathology Department.

He treated an eye infection in two babies with a crude filtrate from a penicillin-producing mould supplied by his lecturer, Alexander Fleming, whilst studying at St Mary's Hospital Medical School in London.

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