Scientists have new hopes of restoring penicillin's full antibiotic effect after discovering how a bacterium which causes pneumonia has become resistant.
The work by UK scientists could also lead to the creation of new designer drugs to tackle diseases such as MRSA.
The University of Warwick team focused on Streptococcus pneumoniae, which kills 5m children a year worldwide.
In recent years, it has been one of a growing number of bacteria which have become resistant to penicillin.
Penicillin, discovered by Sir Alexander Fleming in 1928, became the first widely used antibiotic in the 1940s.
"Solving the problem of penicillin resistance in pneumococci is a key priority for modern medicine and these results provide an important piece in the puzzle"
Penicillin normally acts by preventing the construction of an essential component of the bacterial cell wall called the Peptidoglycan.
This component provides a protective mesh around the otherwise fragile bacterial cell.
The researchers focused on a protein called MurM which has been linked to changes in the chemical make-up of the peptidoglycan observed in patients infected with penicillin-resistant Streptococcus pneumoniae.
They found that the protein acted as an enzyme, playing a key role in the formation of structures within the peptidoglycan which build up its strength.
The higher the levels of MurM activity, the stronger the peptidoglycan became, and the more likely the bacterium would be drug resistant as a result.
Repeated in test tube
The Warwick team, whose study appears in the Journal of Biological Chemistry, were able to replicate the activity of MurM in a test tube, allowing them to study in close detail exactly how it is deployed by Streptococcus pneumoniae to neutralise penicillin.
It is hoped the results will allow researchers to develop new drugs which block bacterial resistance by disrupting the chemistry of MurM.
This could be key not only for Streptococcus pneumoniae, but also for other bacteria, such as MRSA, which also appear to rely on the same chemistry to build resistance.
Researcher Dr Adrian Lloyd said it was possible that new drugs could be developed in two to three years.
He said: "Because we now know in detail what this protein needs to be able to do its job and promote bacterial resistance we should be able to develop drugs to stop it from doing so."
Professor Kevin Kerr, a consultant microbiologist at Harrogate District Hospital, said the findings were interesting, but much more work was needed.
He said: "Solving the problem of penicillin resistance in pneumococci is a key priority for modern medicine and these results provide an important piece in the puzzle.
"The challenge must now be to see if this discovery can be exploited through the identification and development of new drugs which can inhibit this enzyme."
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