Penicillin back in bug war

Research has uncovered how Streptococcus pneumoniae has become resistant to the antibiotic penicillin. The same research could open up MRSA to attack by penicillin and help create a library of designer antibiotics.

Streptococcus pneumoniae causes 5 million fatal pneumonia infections a year in children

The research, led by Dr Adrian Lloyd of the University of Warwick, exposed how the bacteria builds its penicillin immunity and opens up many ways to disrupt that mechanism and restore penicillin as a weapon against these bacteria.

Dr Lloyd said: “Penicillin normally acts by preventing the construction of an essential component of the bacterial cell wall - the Peptidoglycan. We targeted a protein called MurM - key to the formation essential dipeptide bridges within the S. pneumoniae peptidoglycan. The presence of high levels of these dipeptide bridges in the peptidoglycan of Streptococcus pneumoniae is a pre-requisite for high level penicillin resistance.”

The Warwick team were able to replicate the activity of MurM, allowing them to define the chemistry of the MurM reaction in detail and understand every key step of how Streptococcus pneumoniae deploys MurM to gain this resistance.

The results will allow the Warwick team, and any interested pharmaceutical researchers, to target the MurM reaction in a way which will lead to the development of drugs which will disrupt the resistance of Streptococcus pneumoniae to penicillin.

The same research also offers possibilities to disrupt the antibiotic resistance of MRSA which uses similarly constructed peptide bridges in the construction of the peptidoglycan component of its cell wall.

The tools developed at Warwick also open up each step of the creation of the peptidoglycan (MurA, MurB, MurC) used by an array of dangerous bacteria. This provides a valuable collection of targets for pharmaceutical companies seeking ways of disrupting antibiotic resistance in such bacteria.

The team have now established a new network of academics from the fields of chemistry, biology and medicine, as well as pharmaceutical companies to share and exploit this new treasure trove of targets which could help create a range of new designer antibiotic based treatments targeted at a range of bacteria that can cause significant health problems.