Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Typhoid fever bacteria collect on gallstones to perpetuate disease

24.02.2010
A new study suggests that the bacteria that cause typhoid fever collect in tiny but persistent communities on gallstones, making the infection particularly hard to fight in so-called “carriers” – people who have the disease but show no symptoms.

Humans who harbor these bacterial communities in their gallbladders, even without symptoms, are able to infect others with active typhoid fever, especially in developing areas of the world with poor sanitation. The disease is transmitted through fecal-oral contact, such as through poor hand-washing by people who prepare food.

Typhoid fever is rare in the United States, but it affects an estimated 22 million people worldwide, causing symptoms that include a high fever, headache, weakness and fatigue, and abdominal pain. It leads to hundreds of thousands of deaths each year.

Scientists and physicians have known for decades that these bacteria, Salmonella enterica serovar Typhi, accumulate in the gallbladder. In fact, the most widely accepted treatment of chronic typhoid infection is removal of the gallbladder.

“We’re trying to get to the heart of why this is. Why does Salmonella sit in a pool of highly concentrated detergent, which is what bile is, but not die?” said John Gunn, professor of molecular virology, immunology and medical genetics at Ohio State University and senior author of the study. “It’s got to survive in some way, and a good way to survive is by forming a biofilm.”

Biofilms – in this case, the collection of bacteria on gallstones – typically do not respond well to antibiotics or the human immune response. But now that the biofilms themselves have been discovered in association with asymptomatic typhoid infection, they present a potential treatment alternative to expensive and invasive gallbladder removal, Gunn said.

Specifically, targeting a sugar polymer on the bacterial surface that promotes development of the biofilm might be a strategy to prevent biofilm formation in the first place, he said.

The research appears this week in the online early edition of the Proceedings of the National Academy of Sciences.

Gunn and colleagues observed this biofilm formation in mice infected with a strain of Salmonella bacteria similar to the strain that causes typhoid fever in humans. The scientists also detected these biofilms on gallstones in about 5 percent of humans in a Mexican hospital who had their gallbladders removed because of complications from gallstones. Typhoid fever is widespread in Mexico.

“The mouse data coupled with the human data suggest strongly that biofilms lay a foundation that allows for establishment and maintenance of chronic typhoid infection,” said Gunn, also a vice director of Ohio State’s Center for Microbial Interface Biology.

And the researchers suspect biofilms are at play in the gallbladder’s association with typhoid fever because in most cases, the only way to treat a biofilm-related infection is to remove whatever the biofilm has attached to from the body. For example, infections that form on catheters, implanted joints or artificial heart valves typically result from biofilms, and the only way to clear the infection is to remove those devices.

“Information in our lab and in the literature that gallstones were associated with how people became carriers of typhoid bacteria, that organisms were confined to one site, and that antibiotics are ineffective so one has to remove the gallbladder for successful therapy – it all fit with biofilm-related disease,” Gunn said.

In the study, the researchers fed mice either normal food or a high-cholesterol diet for eight weeks, intending to induce gallstones in the animals on the fatty diet. The scientists then gave these mice a type of Salmonella bacteria designed to mimic a chronic human typhoid infection without causing actual illness in the mice. A control group of mice received no bacteria.

The number of bacteria harbored in the gallbladders of mice with gallstones increased over time, becoming abundant within 21 days, and was significantly higher than bacteria in mice that did not have any stones. No bacteria were detected in mice that weren’t given the infection, even if they had gallstones.

In the infected mice, the Salmonella bacteria also could be seen in the gallbladder lining and in bile as well as on the surface of the gallstones. The gallstones were the focus of this study because Gunn’s lab has determined in previous experiments that Salmonellae are attracted to cholesterol-coated surfaces.

There are two common types of gallstones – cholesterol stones and brown or black stones composed primarily of calcium bilirubinate, which can be found in bile. Gunn’s test-tube research to date had suggested that Salmonella Typhi bacteria bind particularly well to cholesterol gallstones to form biofilms, and this current study supported that.

Three weeks after infection, biofilms covered about 50 percent of the surfaces of the gallstones removed from the infected mice.

“What we think is that having gallstones makes you more susceptible to becoming a carrier because it provides that environment for Salmonella to bind to the surface, form a biofilm and establish infection,” Gunn said. “Whether that happens 100 percent of the time, nobody knows.”

In a second component of the mouse study, the researchers tested fresh fecal pellets from infected mice to test the association between gallstone biofilms and transmission of a typhoid-like infection via feces, a phenomenon called “shedding.” The mice with gallstones shed three times more bacteria than did infected mice without gallstones.

“The mice that had gallstones and were infected with bacteria had a much higher rate of shedding, meaning those bacteria were released, probably because they had more bacteria in the gallbladder itself,” Gunn said.

The mouse data not only supported Gunn’s hypothesis that gallstones present at least one surface on which Salmonella biofilms form and maintain the carrier state of typhoid fever. The researchers also realized they had developed a new mouse model for further study of asymptomatic typhoid carriage.

Gunn and colleagues also obtained data from humans at a hospital in Mexico whose gallbladders were removed as a treatment for gallstone complications. Though none of the patients had ever shown symptoms for typhoid fever, 5 percent of them ended up being carriers of Salmonella Typhi bacteria biofilms on their gallstones. In the single patient determined to be a typhoid carrier who didn’t have biofilm on his gallstones, the stones were dark in color, suggesting they were likely composed of something other than cholesterol, Gunn said.

This ability of a single individual to harbor latent bacteria elsewhere in the gallbladder leads Gunn and colleagues to suspect that biofilms can form elsewhere in the gallbladder – perhaps in its lining or persisting within specific cells of the gallbladder wall. Gunn’s lab is exploring those possibilities.

This work is supported by the National Institutes of Health and a graduate education fellowship from Ohio State’s Public Health Preparedness for Infectious Diseases initiative.

Co-authors of the study are Robert Crawford of the Center for Microbial Interface Biology and Department of Molecular Virology, Immunology and Medical Genetics at Ohio State; Roberto Rosales-Reyes and María de la Luz Ramírez-Aguilar of the Universidad Nacional Autonoma de Mexico; Oscar Chapa-Azuela of Hospital General de Mexico; and Celia Alpuche-Aranda of the Instituto Nacional de Referencia Epidemiologica in Mexico.

Contact: John Gunn, (614) 292-6036; gunn.43@osu.edu
Written by Emily Caldwell, (614) 292-8310; caldwell.151@osu.edu

John Gunn | EurekAlert!
Further information:
http://www.osu.edu

More articles from Studies and Analyses:

nachricht Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>