University of Michigan. US: E. coli usually brings to mind food poisoning and beach closures, but
researchers recently discovered a protein in E. coli that inhibits the
accumulation of potentially toxic amyloids—a hallmark of diseases such
as Parkinson's.
Amyloids are formed by proteins that misfold and group together, and
when amyloids assemble at the wrong place or time, they can damage brain
tissue and cause cell death, according to Margery Evans, lead author of
the University of Michigan study, and Matthew Chapman, principal
investigator and associate professor in U-M Molecular, Cellular, and
Developmental Biology.
The findings could point to a new therapeutic approach to Parkinson's
disease and a method for targeting amyloids associated with such
neurodegenerative diseases.
A key biological problem related to patients with Parkinson's is that
certain proteins accumulate to form harmful amyloid fibers in brain
tissues, which is toxic to cells and causes cell death.
While these amyloids are a hallmark of Parkinson's and other diseases
such as Alzheimer's, not all amyloids are bad. Some cells, those in E.
coli included, assemble helpful amyloids used for cell function.
E. coli make amyloid curli on the cell surface, where it's
protective, rather than toxic. The curli anchor the bacteria to kitchen
counters and intestinal walls, where they can cause infections and make
us sick. These helpful amyloids that E. coli produce do not form on the
inside of the cell where they would be toxic.
"It means that something in E. coli very specifically inhibits the
assembly of the amyloid inside the cell. Therefore, amyloid formation
only occurs outside the cell where it does not cause toxicity," said
Evans, a doctoral student in molecular, cellular, and developmental
biology.
Evans and the U-M team went on a biochemical hunt to understand how
E. coli prevented amyloids from forming inside cells and uncovered a
protein called CsgC that is a very specific, effective inhibitor of E.
coli amyloid formation.
U-M researchers have been collaborating with scientists from Umeå
University in Sweden and Imperial College in London, and in the current
study found that the CsgC protein also inhibits amyloid formation of the
kind associated with Parkinson's.
Another implication of the research is that the curli could be a
target for attacking biofilms, a kind of goo created by bacteria, which
acts as a shield to thwart antibiotics and antiseptics. These bacteria
can cause chronic infections, but treating these infections using
molecules that block curli formation may degrade the biofilm and leave
the bacteria more vulnerable to drug therapy.
The study, "The bacterial curli system possesses a potent and
selective inhibitor of amyloid formation," is scheduled to appear Jan.
22 in the online edition of Molecular Cell.
Evans, who conducted the research while at U-M will be a postdoctoral fellow at Washington University in St. Louis.
Other authors include: Fei Li of U-M Molecular, Cellular, and
Developmental Biology; Erik Chorell, Jörgen Åden, Anna Göteson, Pernilla
Wittung-Stafshede and Fredrik Almqvist of Umeå University; Jonathan
Taylor, Marion Koch, Lea Sefer and Steve Matthews of Imperial College
London.
The work was funded in part by the National Institutes of Health.