Global control of Campylobacter jejuni biology by protein lysine acetylation

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Some bacteria get into the food that we eat and cause food-poisoning. Some of these bacteria are quite common but are usually killed during cooking. When chicken meat is not cooked properly, one of these types of bacteria, called Campylobacter jejuni, is a particular problem. It normally lives harmlessly in the intestines of chickens but in humans causes severe diarrohea, which although not usually life-threatening, causes considerable impacts on time off work and in some cases can lead to serious complications. By understanding in detail the way in which this bacterium interacts with both its chicken and human hosts, we may be able to stop colonisation, prevent infection or design better treatments. C. jejuni has a small genome with only about 1650 genes and only a small number of proteins that are known to regulate gene expression. We hypothesise that in this bacterium, the control of the activity of proteins directly, through reversible modifications to their structure by additions of chemical groups, may assume greater importance than in bacteria with large genomes. In this project we wish to investigate one such modification; the addition of acetyl-groups (CH3-CO-) to proteins. We have discovered that over 70% of all of the proteins in C. jejuni are acetylated and that some of these modifications are reversible and controlled by a specific enzyme, a deacetylase. Moreover, we have found that important colonisation determinants such as the ability to swim and assimilate nitrogen for growth are impacted by acetylation. The project will investigate the consequences of acetylation at specific sites in selected proteins in detail and reveal how acetylation is controlled. The results should allow us to get a better knowledge of the way in which the bacterium uses acetylation in the colonisation process and to identify ways of disrupting acetylation, which could be exploited in future to limit its growth in chickens and to treat human infections.