Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery helps mice beat urinary tract infections

19.06.2012
Scientists at Washington University School of Medicine in St. Louis have found new clues to why some urinary tract infections recur persistently after multiple rounds of treatment.

Their research, conducted in mice, suggests that the bacteria that cause urinary tract infections take advantage of a cellular waste disposal system that normally helps fight invaders. In a counterintuitive finding, they learned that when the disposal system was disabled, the mice cleared urinary tract infections much more quickly and thoroughly.

"This could be the beginning of a paradigm shift in how we think about the relationship between this waste disposal system, known as autophagy, and disease-causing organisms," says senior author Indira Mysorekar, PhD, assistant professor of obstetrics and gynecology and of pathology and immunology. "There may be other persistent pathogens that have found ways to exploit autophagy, and that information will be very useful for identifying new treatments."

The results will be published the week of June 18, 2012, in the early online edition of The Proceedings of the National Academy of the Sciences.

Urinary tract infections are very common, particularly in women. In the United States alone, annual treatment costs are estimated to run as high as $1.6 billion. Scientists believe 80 percent to 90 percent of these infections are caused by the bacterium Escherichia coli (E. coli).

Data from the new study and earlier results have led Mysorekar and her colleagues to speculate that E. coli that cause recurrent urinary tract infections may hide in garbage-bin-like compartments within the cells that line the urinary tract.

These compartments, found in nearly all cells, are called autophagosomes. They sweep up debris within the cell, including harmful bacteria and worn-out cell parts. Then, they merge with other compartments in the cell that are filled with enzymes that break down the contents of autophagosomes.

"We think, but can't yet prove, that the bacteria have found a way to block this final step, " Myosrekar says. "This would transform the autophagosome from a death trap into a safe haven where the bacteria can wait, hidden from the immune system, for their next chance to start an infection."

In the new research, Mysorekar teamed with colleagues at the School of Medicine who had developed mice in which both copies of an important autophagy gene, Atg16L1, were impaired. Co-author Herbert W. Virgin, MD, PhD, Edward Mallinckrodt Professor and head of the Department of Pathology and Immunology, and others created the mice to study Crohn's disease, a chronic bowel inflammation associated with mutations in Atg16L1.

Co-lead authors Caihong Wang, DVM, PhD, a staff scientist, and Jane Symington, an MD/PhD student in the Mysorekar group, infected the mice with E. coli. The researchers found that bacteria levels in the urinary tracts of the modified mice decreased much more rapidly after infection than they did in normal mice. Cells lining the urinary tract in mice with the mutated gene also had significantly fewer dormant reservoirs of E. coli than in normal mice.

The scientists identified structural changes in urinary tract cells of the mice with Atg16L1 mutations that may help explain their unexpected results. These changes may have made it much more difficult for the bacteria to find and break into autophagosomes, Mysorekar says.

The altered gene also was associated with changes in the immune system. In the modified mice, E. coli infections in the urinary tract led cells to produce more inflammatory immune factors and prompted additional bacteria-fighting immune cells to come to the site of the infection.

"The immune system appears to be primed to attack at the slightest provocation in the mice with mutations," Mysorekar says. "This may be why mutations in Atg16L1 are also connected with Crohn's disease, which involves immune cells erroneously attacking beneficial microorganisms in the gut."

Mutations in Atg16L1 are quite common, according to Virgin, although not everyone who has a mutated form of the gene will get Crohn's disease.

"These new results may help explain why the mutations have persisted for so long in the general population," he says. "They don't just put the carrier at risk of Crohn's disease, they also may have a protective effect that helps fight infections."

Mysorekar plans to investigate how E. coli takes advantage of a fully functioning autophagy system in mice with urinary tract infections.

Wang C, Mendonsa GR, Symington JW, Zhang Q, Cadwell K, Virgin HW, Mysorekar IU. Atg16L1 deficiency confers protection from uropathogenic Escherichia coli infection in vivo. The Proceedings of the National Academy of Sciences, early online edition, week of June 18, 2012.

Funding from National Institute of Child Health and Human Development Grant T32-54560 (to G.R.M.), U54AI057160, Project 5 (to H.W.V.) and K99/R00 Pathway to Independence Award DK080643 (to I.U.M.) supported this research.

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 sixth 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 Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>