St.
Louis, MO (8/12/99)- The first ever three dimensional images of the steps
involved in bacterial infection provide clues to a whole new way to ward off
infectious diseases.
A St. Louis research team obtained X-ray crystallography images that might
aid in the fight against bladder and kidney infections. Many infectious bacteria
have hair-like fibers, known as pili, on their surfaces that enable them to
attach themselves to a host. Hultgren's team was able to obtain imaging data
showing how a class of proteins known as chaperones facilitate the process
of pili assembly.
Left: Pili
formation (click for entire image)
"These are the first detailed snapshots of the basis for an interaction between
a disease-causing bacterium and its host," says Scott J. Hultgren, Ph.D.,
professor of molecular microbiology at Washington University School of Medicine
in St. Louis.
Infectious bacteria such as E.coli depend on pili to attach to human cells.
Without them, the bacteria cannot cause infections. This suggests that preventing
the formation of pili should be an effective antimicrobial strategy,e noted.
Hultgren's team identified several major components of pilus assembly. These
include: protein subunits that eventually are assembled into pili; boomerang-shaped
proteins called chaperones that ferry the subunits to the bacterial cell surface;
and doughnut-shaped proteins called ushers that assemble and extrude pili.
The current research involved determining the crystal structure of E.coli
proteins involved in bladder and kidney infections. However, the research
has implications for the treatment of many other infections caused by pili-bearing
bacteria, including middle-ear infections, pneumonia, meningitis and gonorrhea.
Hultgren is collaborating with a pharmaceutical company to develop therapeutics
that will block the formation of bacterial pili and which therefore would
be useful in the prevention and treatment of bacterial infections in humans.
A vaccine designed to foil pili formation in E.coli effectively blocked infection
in studies with mice.
"But what we're really excited about is that these principles might apply
to a wide range of biological fibers, such as the amyloid fibers that are
important in Alzheimer's disease and the prion proteins associated with mad-cow
disease and Creutzfeldt-Jakob syndrome. Therefore, we hope our findings will
stimulate many new lines of research," said Hultgren.
Dr. Hultgren's lab collaborated with Swedish researchers Stefan D. Knight,
Ph.D. and Devapriya Choudhury, Ph.D., both at Uppsala Biomedical Center. The
research appears in the Aug. 13.1999 issue of Science.
Copyright 1999© Info
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