European researchers have identified 39 proteins that interact with bacterial toxins in infected human cells, amounting to significant progress in understanding bacterial infection sources. The discovery, funded in part by the EU through the 'Interaction proteome' project, may open up new treatment targets for human illnesses in the future. The study is published in the journal Cell Host and Microbe.
Many bacteria, which can enter the body through the touch of a simple door handle, for example, produce toxins that can damage invaded human cells. Several bacteria introduce toxins into human cells using a system that acts somewhat like a molecular syringe. Once inside the host cell, some of these toxins disturb vital cellular signalling pathways involved in major processes like cell division. These pathways are controlled largely by simple protein-protein interactions. Bacteria can then multiply and stay alive by abusing the human host's cell machinery.
The new research findings represent a considerable step forward since, until now, only a few of the proteins that interact with these toxins had been documented by scientists. With the help of a new method developed by Professor Matthias Mann of the Max Planck Institute (MPI) in Germany using high-resolution mass spectrometry, the scientists were able to screen for several proteins at once by examining the cellular target sites of the toxins.
The team used quantitative proteomics to harness their results. Quantitative proteomics, which aims to generate quantitative information on all proteins in a study, is recognised as a powerful way of studying protein-protein interactions (interactions that are believed to play a key role for molecular pathogenesis of infectious diseases).
Dr Matthias Selbach of the Max Delbrück Center for Molecular Medicine (MDC) in Germany was surprised to discover that the toxins have not necessarily adapted to the structures of the human proteins in the best way possible; in fact they bind rather weakly to each human protein. Nevertheless, they can influence many proteins simultaneously.
"A single bacterial toxin seems to function like a master key that can access different host cell proteins in parallel," explained Dr Selbach. "Perhaps it is due to this strategy that bacteria are able to attack very different cells and, thus, to increase their survival chances in the host." Dr Selbach suggests that the team's results could contribute to the development of better ways of treating bacterial infections, such as new drugs aimed at the signalling mechanisms that are disrupted by the toxins.
'Interaction proteome' is an Integrated Project under the 'Life sciences, genomics and biotechnology for health' Theme of the Sixth Framework Programme (FP6). With EUR 12 million in funding support from the European Union, it is the largest proteomics project in FP6. The EU provides considerable support to research in proteomics, a term combining the words 'protein' and 'genome', used to define the field that studies proteins (e.g. their functions and structures) produced by cells in large scale and that requires highly efficient technology.
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