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Deceiving cell walls
Date:1/28/2009

This release is available in German.

Approximately 1.6 million people die worldwide every year as a result of pneumococcal infection, which causes grave illnesses, including pneumonia, meningitis, and middle-ear infections. Children and the elderly are especially at risk. Vaccines are only effective against a few of the pneumococcal types and increasing resistance to antibiotics is making treatment more difficult. Researchers led by Jess M. Sanz at the Miguel Hernandez University (Elche, Spain) and Maarten Merkx at the Eindhoven University of Technology (Netherlands) have now introduced a highly promising new approach for the development of drugs to treat pneumococci. As they report in the journal Angewandte Chemie, the scientists copied the choline architecture of the pneumococcal cell wall. They were thus able to trap the choline-binding proteins that have a critical effect on the infectiousness of pneumococcal bacteria.

The cell walls of pneumococci contain special polymers, called teichoic acids, that are equipped with phosphocholine groups and induce a characteristic choline architecture on the cell walls. The choline groups act as docking stations for a number of special proteins that are involved in important processes such as cell-wall division, the release of bacterial toxins, and adhesion to infected tissues. These choline-binding proteins (CBP) contain domains with multiple neighboring choline-binding sites. The protein LytA, for example, has a domain with four choline-binding sites.

If choline is added to a culture of pneumococci, the molecules occupy the choline binding sites of the CBPs so that the proteins can no longer bind to the cell walls of the pneumococci. Although the bacteria continue to multiply, the individual cells can no longer separate from each other, which results in long chains of linked cells. In addition, the
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Contact: Jess M. Sanz
jmsanz@umh.es
34-966-658-460
Wiley-Blackwell
Source:Eurekalert  

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