A new study shows how two strains of the intestinal bug E. coli manage to hijack host proteins used to control the body’s immune system.
The research shows how E. coli bacteria can block key human enzymes, in a way that has not previously been shown in any other biological context.
The enzymes, known as kinases, are molecular switches that control processes such as immune responses to infection and cancers in humans. Better understanding how the E. coli bacteria interfere with kinases will provide valuable avenues for investigating new therapies.
There are many different strains of E. coli. While some are good bacteria, others can cause symptoms ranging from mild diarrhoea and nausea to kidney failure and death. The two strains examined in this study are E. coli O157, which causes food-borne infections, and enteropathogenic E. coli (EPEC), which is a major cause of infantile diarrhoea in low-income countries.
At present there are no vaccines or effective drugs to combat these infections – in fact antibiotic treatment of E. coli O157 infection can cause the invading bacteria to release more toxins, making the symptoms worse. Patients are treated with fluids and nutrients to enable their immune system to fight the infection.
One reason why these strains are so dangerous is that they inject bacterial proteins into human cells. These proteins hijack the cell’s signalling network to promote their growth and survival, for example by preventing the host from recognising them as harmful bacteria.
The new research found that E. coli O157 and EPEC inject a protein called EspJ which inhibits the kinases from signalling.
“The way in which the EspJ protein blocks the activity of human kinases is completely novel,” says Professor Gad Frankel , from the MRC Centre for Molecular Bacteriology and Infection. “This study will help us better understand how pathogens are able to hijack cells and how they prevent the immune system from fighting the infection.”
The team reached their conclusions after performing biochemical, mass spectrometry and cell biology assays. This study provides valuable new avenues of investigation: further research will look at whether EspJ-like proteins in other intestinal pathogens, such as Salmonella, behave in similar ways, and also what effect EspJ proteins in E. coli O157 might have on other types of kinases.
The research was carried out by a team of scientists at Imperial College London, working in collaboration Albert-Ludwigs-Universitšt Freiburg, in Germany.
Reference: ’The Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation’, Joanna Young, Abigail Clements, Alexander E. Lang, James A. Garnett, Diana Munera, Ana Arbeloa, Jaclyn Pearson, Elizabeth L. Hartland, Stephen J. Matthews, Aurelie Mousnier, David J. Barry, Michael Way, Andreas Schlosser, Klaus Aktories and Gad Frankel. Nature , 19 December 2014. doi: 10.1038/ncomms6887