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How bacteria trick each other in their math

Researchers reveal how bacterial signal molecule is destroyed

Oeiras, 06.04.11

The Bacterial Signalling laboratory (IGC/ITQB), the Centro de Ressonância Magnética António Xavier and the Bioorganic Chemistry and Organic Synthesis laboratories at ITQB, in collaboration with the Swarthmore College in Pennsylvania, have just revealed how Escherichia coli destroys the signal molecule used by several species of microorganisms for bacterial communication, tricking them in their population math. The work is published in the Journal of Biological Chemistry.

Many bacteria have a way of knowing how many they are through a process called quorum sensing. By regulating gene expression according to their population density, bacteria are able to coordinate important behaviours such as biofilm formation and the production of virulence factors. Quorum sensing is mediated by signal molecules called autoinducers. Autoinducer-2 (AI-2), is produced by many species of bacteria and can also facilitate inter-species cell-cell signalling. But certain bacteria (like E. coli and Salmonella typhimurium) are able to process the signal, thus, quenching inter-species communication and fooling other members of the bacterial community as to determining their real numbers.

How the production of Al-2 molecule is regulated has been known for some time - it is a virtuous circle in which the concentration of AI-2 stimulates its own production - but its degradation was still not clear. Now, using in vivo and in vitro NMR, researchers show that the first step in the catabolic reaction in E. coli is the isomerisation of the phosphorylated signal molecule into an unstable intermediate (3,4,4-trihydroxy-2-pentanona-5-phosphate). The X-ray structure of this new isomerase allowed determining its active site, which was confirmed by site-directed mutagenesis.

This discovery may pave the way into new methodologies of quenching the interspecies signalling mechanisms, which can be of great utility in the development of therapies to control bacterial behaviour.

Original Article

J. Biol. Chem. published March 30, doi:10.1074/jbc.M111.230227

Processing the inter-species quorum sensing signal Autoinducer-2: characterization of Phospho-DPD isomerization by LsrG

João C. Marques, Pedro Lamosa, Caitlin Russell, Rita Ventura, Christopher Maycock, Martin F. Semmelhack, Stephen T. Miller and Karina B. Xavier

João C. Marques and Karina B. Xavier - Instituto Gulbenkian de Ciência and Instituto de Tecnologia Química e Biológica

Pedro Lamosa, Rita Ventura - Instituto de Tecnologia Química e Biológica

Christopher Maycock - Instituto de Tecnologia Química e Biológica and Faculdade de Ciências da Universidade de Lisboa

Caitlin Russell and  Stephen T. Miller - Swarthmore College, Pennsylvania

Martin F. Semmelhack - Princeton University

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