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E. coli bacteria make Alzheimers-linked fibers

wth of the snowflake.

Curli production in E. coli involves two main proteins, CsgA and CsgB. The A protein is released by the bacteria dissolved in the surrounding fluid. The B molecule is embedded in the wall of the bacterium and is exposed to the outside. Like dust particles in snowflake production, each B protein is a nucleus that triggers the precipitation of dissolved A-proteins. As the A proteins pop out of solution they join together and align into curli fibers, with each fiber attached to a B protein.

The finding also raises the important question of whether bacterial infections play some role in amyloid diseases, including Alzheimers disease.

Human amyloid diseases also are thought to involve dissolved amyloid proteins that undergo a change in shape and aggregate into fibers, says Hultgren. When those fibers develop in the brain, it leads to Alzheimers disease. According to Hultgren, the question is, what causes the soluble protein in human disease to convert into amyloid fibers? We can now study that mechanism in E. coli.

Hultgren and Chapman speculate that bacterial infections could play a role in the development of amyloid plaques in Alzheimers disease and other amyloid diseases in at least two ways.

Bacteria might contribute directly to plaque formation through the amyloid they produce, says Chapman, or they might contribute indirectly by triggering the precipitation of amyloid precursor proteins already present in the body. Hultgren and his research team also are working to crystallize the combined A and B proteins to visualize how the two molecules interact.

Learning that bacteria produce amyloid is a revelation, says Paul Berg, Cahill Professor of Cancer Research and Biochemistry, Emeritus, at Stanford University School of Medicine and winner of the 1980 Nobel Prize in Chemistry.

That discovery provides an additional vantage point from which to assess the role of amyloid production and
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Contact: Darrell E. Ward
wardd@msnotes.wustl.edu
314-286-0122
Washington University School of Medicine
31-Jan-2002


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