Investigation into Alzheimer’s disease appears as an improbable approach to yield a better way to fight urinary tract infections (UTIs). However, that’s what scientists at Washington University School of Medicine in St. Louis seemed to have reported.
One element is known to link the different areas of study that is amyloids, which are fibrous, sticky protein aggregates. Some infectious bacteria apparently make use of amyloids to attach to host cells and to build biofilms. Biofilms are known to be bacterial communities bound together in a film that helps resist antibiotics and immune attacks. Amyloids may also be formed inside the nervous system in Alzheimer’s disease, Parkinson’s disease and many other neurodegenerative disorders.
In order to probe amyloids’ contributions to neurodegenerative diseases, scientists were believed to have altered possible UTI-fighting compounds. These compounds seemed to have been initially chosen for their ability to block bacteria’s ability to create amyloids and form biofilms. However, when they brought the compounds back to UTI study after the neurology studies, they found the changes appeared to have also suddenly 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 National Institutes of Health has estimated that over 80 percent of microbial infections are caused by bacteria growing in a biofilm. Scientists in Hultgren’s laboratory were noted to have worked for decades to recognize 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. 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.†says co-lead author Jerome S. Pinkner, laboratory manager for Hultgren.
Co-lead author Matthew R. Chapman, Ph.D., now associate professor of molecular, cellular and developmental biology at the University of Michigan, a postdoctoral fellow in Hultgren’s lab in 2002 was believed to have discovered the same bacterium that causes most UTIs, Escherichia coli, intentionally making amyloids. The amyloids appear to go into fibers known as curli that are extruded by the bacteria to strengthen the structures of biofilms.
For the purpose of treating UTIs, study authors seemed to have developed compounds that block bacteria’s ability to make curli. This may in turn disrupt their ability to make biofilms and leave them more susceptible to antibiotics or immune system attacks. The authors were of the opinion that altering a group of the most promising curli-blockers could be done in order to see if they can also block the processes that form amyloids in Alzheimer’s disease.
The authors found that the alterations seemed to have worked. In laboratory tests, the novel compounds appeared to have prevented the protein fragment known as amyloid beta from culminating into amyloid plaques. Supposedly, amyloid plaques appear like those found in the brain in Alzheimer’s disease.
Chapman further said that, “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.â€
Further, the team was observed to have taken the novel compounds back to a mouse model of UTIs. They found that the altered compounds seemed to have been better at decreasing the virulence of infections. Apparently, this inhibited 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,†says Hultgren.
Chapman cautions that it’s too early to tell which, if any, of the compounds will be useful in treating neurodegenerative diseases. Currently, Hultgren along with his colleagues are noted to be developing even more strong infection and amyloid fighters. Moreover, they seemed to be screening a library of thousands of chemicals similar to the most promising compounds from the study.
The findings of the study have been published in the journal, Nature Chemical Biology.