Plaques With a Purpose: Useful fibers in bacteria resemble deadly protein clumps (Alzheimer's disease)

Abstract

Bacteria spin fibrous webs of protein that allow them to attach to a variety of surfaces. These fibers, new research shows, are surprisingly similar to the misshapen proteins that compose the plaques that characterize Alzheimer's disease. The microbes might lead researchers to a deeper understanding of fiber formation and provide hints about how to keep the troublesome tendrils under control in human brains. The bacterium Escherichia coli spits out copies of a protein called CsgA that link together into extended filaments called curli fibers. The fibers help the bacteria bind to surfaces: Without curli fibers, E. coli cells can't attach to the protein meshwork that coats mammalian tissues and don't form the antibiotic-resistant bacterial communities known as biofilms that foul sewer pipes and cause maladies such as gum disease. Curli fibers appear tangled when viewed under a microscope, and they are impervious to harsh chemical treatments that dissolve most proteins. Those observations suggested to Chapman and colleagues that they might resemble the stubborn amyloid fibers that gum up brains of Alzheimer's patients. To further investigate the similarity, the researchers examined the properties of curli fibers purified from E. coli grown on a petri dish. Measurement of polarized light shone through the fibers indicated that the proteins adopt a so-called β-sheet structure typical of amyloid fibers. In addition, the purified curli fibers soak up two molecular labels--Congo red and thioflavin T--as amyloid fibers do. And once bound to curli fibers, these compounds exhibit the same shift in their fluorescent properties that they display when bound to amyloid fibers. The results suggest that the bacterial curli fiber and the human amyloid fiber form related structures even though they consist of different protein building blocks. Although the human amyloid protein readily coalesces on its own, CsgA forms fibers only with the help of other E. coli proteins. For instance, bacteria that lack the CsgB protein spew out CsgA molecules that don't aggregate. CsgB seems to snap CsgA into a form that can latch onto other copies of CsgA and build curli fibers. The authors suggest that E. coli might use these auxiliary molecules to ensure that CsgA doesn't polymerize until it is outside the cell. Scientists have traditionally viewed amyloid fibers as aberrant structures that result from protein-folding mishaps; although they've suspected that amyloid protein also performs a useful biological chore, that function has escaped detection. The new work uncovers one example of an amyloid-like fiber that serves a deliberate purpose. The benefit it provides could explain why proteins that clump together like amyloid haven't disappeared over the course of evolution. Analyzing the bacterial curli fibers could help scientists get a handle on the molecular principles that govern amyloid protein clumping, a task that has foiled researchers who study the mammalian aggregates. If those rules apply generally, they might lead to new treatments that stop amyloids from littering human brains. --R. John Davenport M. R. Chapman, L. S. Robinson, J. S. Pinkner, R. Roth, J. Heuser, M. Hammar, S. Normark, S. J. Hultgren, Role of Escherichia coli curli operons in directing amyloid fiber formation. Science 295 , 851-855 (2002). [Abstract] [Full Text]