E. coli Bacteria Make Alzheimer’s-linked Fibers

New research from the Washington University School of Medicine in St. Louis has shown fibers known to be important in Alzheimer’s disease are also produced by bacteria that cause ailments and infections. The finding are published in the February 1 issue of the journal Science.

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 plaque, 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 Scott J. Hultgren, Ph.D., the Helen Lehbrink Stoever Professor of Molecular Microbiology, and leader of the study. “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.”

The finding also raises the important question of whether bacterial infections play some role in amyloid diseases, including Alzheimer’s disease. Human amyloid diseases are also thought to involve dissolved amyloid proteins that undergo a change in shape and aggregate into fibers, Hultgren said. When those fibers develop in the brain, it leads to Alzheimer’s disease.

“Bacteria might contribute directly to plaque formation through the amyloid they produce,” said Matthew R. Chapman, Ph.D., post-doctoral fellow in molecular microbiology and first author, “or they might contribute indirectly by triggering the precipitation of amyloid precursor proteins already present in the body.”

“Learning that bacteria produce amyloid is a revelation,” said 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 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.”

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