New research from the University of Sheffield has identified an ‘off’ switch for bacterial growth

New research from scientists at the University of Sheffield has identified a protein switch that can effectively ‘switch off’ growth of an infectious bacteria.

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The new study, led by researchers from the Department of Molecular Biology and Biotechnology, in collaboration with Harvard Medical School (Boston, USA) and CNRS (Lyon, France) discovered a new protein, MacP, which bacteria use to control cell wall building machinery.

This discovery helps us to understand the highly coordinated process that is bacterial growth, raising the possibility that similar ‘protein switch’ mechanisms could occur across bacterial species and if exploited correctly, could limit cell wall growth and spell disaster for growing bacteria in an infection.

Most infectious bacteria are surrounded by a strong cell wall that protects them from breakage. Penicillin, and similar antibiotics have been used to treat serious infections for decades by compromising the strength of the cell wall, killing the bacteria and hopefully saving the patient. Penicillin works by selectively ‘shutting down’ a critical component in a large machine that is constantly building new cell wall as the bacteria grow.

Researchers set out to investigate how the cell wall building machinery is controlled in the bacterium Streptococcus pneumoniae, which causes serious infections like pneumonia, sepsis and meningitis using a DNA sequencing technique to search for new genes involved in the cell wall construction pathways. Through this work the discovery of the MacP protein was made; the new component that’s required for key functions of the cell wall building process, which acts as an ‘on/off switch’.

The study also shows what processes drive this switching event and revealed a long sought-after link between cell wall synthetic (building) activities and an important regulatory network in the S. pneumoniae cell.

Lead author, Dr Andrew Fenton, Research Fellow in the Department of Molecular Biology and Biotechnology said: “The last few years has seen a revolution in the way we think about cell wall growth in bacteria. Recent findings have redefined the biochemical activities of many factors we thought we understood. This paradigm shift has opened many exciting lines of investigation, including how the cell wall building machinery is regulated.

“It is now clear that different types of bacteria approach the regulation of cell wall growth in different ways. This study breaks new ground in our understanding and links cell wall growth to central regulatory processes within the bacterial cell.

“With bacteria pushing back against antibiotic treatment there is an ever-increasing burden on current clinical practices. Cell wall growth remains one of most widely used targets when treating bacterial infections. Therefore, there has never been a more urgent need for us to understand these processes.”

This finding links cell wall growth to many other developmental processes within the cell and further work will help us to understand how the MacP-switch operates and, ultimately, what signals trigger the function of the cell wall building machines.

The full paper entitled: Phosphorylation-dependent activation of the cell wall synthase PBP2a in Streptococcus pneumoniae by MacP has been published today in PNAS (Proceeding of the National Academy of Sciences).

View the full paper