AMHERST, Mass. Biochemist Alejandro Heuck at the University of Massachusetts Amherst recently received a five-year, $950,000 grant from the National Institutes of Health to map the molecular structure of a needle-like tool used by deadly bacteria to drill holes in mammalian cell walls.
Once a channel is open, bacteria that cause such diseases as bubonic plague (Yersinia pestis), dysentery (Shigella), food poisoning (Salmonella) and sepsis (Pseudomonas aeruginosa) pump proteins in to destroy the body's ability to fight infection, killing millions each year worldwide. The researchers hope this advance will help to identify new targets for developing new drugs and treatment avenues
The new studies will build on a breakthrough reported last year by graduate student Fabian Romano and Heuck (pronounced Hoik), who were able to characterize enough of the bacterial needle to build a model membrane system for further experiments. This will let them study how the molecular machine known as the Type III secretion system (T3S) pokes holes, or translocons, in cell walls of warm-blooded animals and humans to inject toxic proteins.
The T3S system is used by many pathogens, but the UMass Amherst team will study it in Pseudomonas aeuginosa because unlike many bacteria, this one has only one T3S system, allowing for experiments with fewer variables. This strain of Pseudomonas causes sepsis, which easily develops resistance to antibiotics. Also, because it can infect so many different organisms from roundworms to mice to people, Pseudomonas studies conducted in a glass culture dish can be readily tested in more complex organisms.
Heuck recalls that last year's breakthrough successfully opened the door to the current work by solving "a very difficult puzzle." He adds, "It took a lot of experiments to understand how these water-soluble, water-loving proteins in the T3S translocon system could suddenly transform themselves drastically, enou
|Contact: Janet Lathrop|
University of Massachusetts at Amherst