E. Coli Bacteria Make Alzheimer’s-Linked Fibers

[Guest guest]

Source: Washington University School Of Medicine

(http://medinfo.wustl.edu/)

Date: Posted 2/1/2002

E. Coli Bacteria Make Alzheimer’s-Linked Fibers

Fibers known to be important in Alzheimer’s disease also are produced by

bacteria that cause ailments such as urinary tract infections, according to

research at Washington University School of Medicine in St. Louis. The

finding is described in the February 1 issue of the journal Science.

J. Hultgren, Ph.D., the Helen Lehbrink Stoever Professor of Molecular

Microbiology, led the study; R. Chapman, Ph.D., post-doctoral fellow

in molecular microbiology was first author.

The scientists found that certain strains of the bacterium Escherichia coli

(E. coli) produce amyloid fibers similar to those that can accumulate in the

brain to form senile plaques, a hallmark of Alzheimer’s disease. The

bacterial fibers, known as curli, form a meshwork around the bacteria,

joining them together in clusters or communities known as biofilms. Bacteria

in biofilms are more resistant to antibiotics and to the body’s immune

defenses.

The discovery marks the first time that amyloid has been found in bacteria.

Previously, amyloid was thought to be made only by cells of higher

organisms. Even then, their presence was regarded as a mistake, a biological

error.

“This is the first example of a dedicated molecular machinery to produce

amyloid and thus shows that amyloid production is not always a mistake,”

says Hultgren. “This finding gives us a powerful genetic system to study the

molecular details of amyloid formation and may allow us to begin designing

drugs that will block the formation of amyloid or treat or prevent human

amyloid diseases.”

Salmonella bacteria also produce bacterial amyloid or curli, and the genes

for curli production exist in other bacteria, as well, says Chapman. The

process of curli production is similar to the formation of a snowflake on a

dust particle. The particle is a nucleus that triggers the precipitation of

ice crystals at its surface, setting off a chain reaction that leads to more

ice crystals and growth 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 Alzheimer’s

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 Alzheimer’s

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 Alzheimer’s 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 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 accumulation in Alzheimer's disease and

related neuro-pathologies. Hopefully, this model will reveal clues for

preventing the devastating formation of amyloid plaques characteristic of

those diseases. "

Editor's Note: The original news release can be found at

http://mednews.wustl.edu/medadmin/PAnews.nsf/0/1974AC8F1FE2B59286256B5000619619

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Note: This story has been adapted from a news release issued by Washington

University School Of Medicine for journalists and other members of the

public. If you wish to quote from any part of this story, please credit

Washington University School Of Medicine as the original source. You may

also wish to include the following link in any citation:

http://www.sciencedaily.com/releases/2002/02/020201080207.htm

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