Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Alzheimer's research sheds light on potential treatments for urinary tract infections

27.11.2009
Research into Alzheimer's disease seems an unlikely approach to yield a better way to fight urinary tract infections (UTIs), but that's what scientists at Washington University School of Medicine in St. Louis and elsewhere recently reported.

One element links the disparate areas of research: amyloids, which are fibrous, sticky protein aggregates. Some infectious bacteria use amyloids to attach to host cells and to build biofilms, which are bacterial communities bound together in a film that helps resist antibiotics and immune attacks. Amyloids also form in the nervous system in Alzheimer's disease, Parkinson's disease and many other neurodegenerative disorders.

To probe amyloids' contributions to neurodegenerative diseases, scientists altered potential UTI-fighting compounds originally selected for their ability to block bacteria's ability to make amyloids and form biofilms. But when they brought the compounds back to UTI research after the neurology studies, they found the changes had also unexpectedly made them more effective UTI treatments.

"Thanks to this research, we have evidence for the first time that we may be able to use a single compound to impair both the bacteria's ability to start infections and their ability to defend themselves in biofilms," says senior author Scott J. Hultgren, Ph.D., the Helen L. Stoever Professor of Molecular Microbiology at Washington University.

The findings were reported online in Nature Chemical Biology.

The National Institutes of Health has estimated that over 80 percent of microbial infections are caused by bacteria growing in a biofilm, according to Hultgren. Scientists in Hultgren's laboratory have worked for decades to understand the links between biofilms and UTIs.

"UTIs occur mainly in women and cause around $1.6 billion in medical expenses every year in the United States," says co-lead author Jerome S. Pinkner, laboratory manager for Hultgren. "We think it's likely that women who are troubled by recurrent bouts of UTIs are actually being plagued by a single persistent infection that hides in biofilms to elude treatment."

Co-lead author Matthew R. Chapman, Ph.D., now associate professor of molecular, cellular and developmental biology at the University of Michigan, was a postdoctoral fellow in Hultgren's lab in 2002 when he discovered that the same bacterium that causes most UTIs, Escherichia coli, deliberately makes amyloids. The amyloids go into fibers known as curli that are extruded by the bacteria to strengthen the structures of biofilms.

To treat UTIs, Hultgren's lab has been working with Fredrik Almqvist, Ph.D., a chemist at the University of Umea in Sweden, to develop compounds that block bacteria's ability to make curli, disrupting their ability to make biofilms and leaving them more vulnerable to antibiotics or immune system attacks. Almqvist recently suggested altering a group of the most promising curli-blockers to see if they could also block the processes that form amyloids in Alzheimer's disease.

The alterations worked: In laboratory tests, the new compounds prevented the protein fragment known as amyloid beta from aggregating into amyloid plaques like those found in the brain in Alzheimer's disease. When scientists took the new compounds back to a mouse model of UTIs, though, they received a surprise. The altered compounds were better at reducing the virulence of infections, inhibiting not only curli formation but also the formation of a second type of bacterial fibers, the pili.

"Pili aren't made of amyloids, but they are essential to both biofilms and to the bacteria's ability to initiate an infection," Hultgren says.

Hultgren and colleagues are already developing even more potent infection and amyloid fighters, screening a library of thousands of chemicals similar to the most promising compounds from the study.

Chapman cautions that it's too early to tell which, if any, of the compounds will be helpful in treating neurodegenerative diseases.

"Much neurodegenerative drug development has focused on ways to break up amyloids or prevent them from forming, but because amyloids may also be an important part of normal cellular physiology, we need to identify molecules that will target only the toxic amyloid state," he says.

Cegelski L, Pinkner JS, Hammer ND, Cusumano CK, Hung CS, Chorell E, Aberg V, Walker JN, Seed PC, Almqvist F, Chapman MR, Hultgren SJ. Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation. Nature Chemical Biology, published online.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

Construction of practical quantum computers radically simplified

05.12.2016 | Information Technology

NASA's AIM observes early noctilucent ice clouds over Antarctica

05.12.2016 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>