Sunday, June 20, 2010

Pneumococcal Fratricides

 Excerpts from César Sánchez's blog
Some bacteria produce substances that kill surrounding microbes, and use the resulting dead bodies as a source of nutrients. Sometimes, killer and victim belong to the same species, or even they are siblings. In these cases, researchers speak of cannibalism or fratricide; although if you view microbial populations as coordinated, multicellular entities, then you may prefer to use the term programmed cell death.
Among pneumococci, some cells in a population become competent in response to certain signals; which means that they are able to take up DNA from their surroundings, and incorporate this genetic information into their own chromosome. This way, competent cells can acquire new inheritable abilities—such as production of a new capsule type, or resistance to an antibiotic—that can be very important for their survival. (This was the underlying mechanism in the famous Avery-MacLeod-McCarty experiment that helped identify DNA as the hereditary material in cells.)
But competent pneumococci do something else: they encourage non-competent siblings and other closely-related bacteria to commit suicide. They do this by releasing a particular lytic enzyme, called CbpD, that diffuses through the milieu and—somehow—activates LytC and other lytic enzymes that are already present in the non-competent siblings. Cell wall weakening finally results in a big bang: that is, the explosion of the non-competent pneumococci. The materials released serve not only as nutrients and sources of genetic information (DNA), but also as virulence factors that help competent cells to survive in their human host.

The structure of the pneumococcal
autolysin, LytC. Source.
The 3D structure of LytC now provides the clues to explain the enzyme's peculiar behaviour during pneumococcal fratricide. Have a look at the model of LytC on the right: ain't it a beauty? A substrate-binding module (in blue and green in the image) recognizes and binds the cell wall peptidoglycan, whereas a catalytic module (in red) is responsible for breaking a specific linkage in the substrate. Because of the unusual hook shape of the protein, the substrate-binding module and the catalytic module partially block each other. As a result, LytC cannot bind the highly cross-linked peptidoglycan that is predominant under normal circumstances. Only when CbpD or other lytic enzymes cut specific linkages in the cell wall, LytC is able to bind the 'loosened' peptidoglycan and comes into action—with deleterious consequences for the non-competent pneumococci.