'Gut'-throat competition: Research on digestive tract bacteria yields surprising findingsMay 11, 2012
ANN ARBOR, Mich. - From tiny villages in developing nations to suburban kitchens in the United States, dangerous strains of E. coli bacteria sicken millions of people each year - and kill untold numbers of children.
Now, new research from the University of Michigan Health System gives scientists a better understanding of what is going on in the diarrhea-wracked guts of its victims, and what might be done to prevent or treat it.
Specifically, they show that the bacteria that usually live in our digestive tracts compete against invading bacteria such as E. coli to help our bodies fend them off.
They also show that the invaders depend on certain genes to gain a temporary upper hand in that battle -- just long enough to reproduce and cause the symptoms that expel their offspring from the body so they can find a new host.
The findings, published in journal Science on its Science Express website, point to potential ways to prevent or treat infections by enterohemorrhagic or enteropathogenic E. coli. Those are the types that can lurk in undercooked ground beef, unpasteurized milk, untreated drinking water, and contaminated produce - and that can cause diarrhea and other symptoms that sicken adults and can kill vulnerable children.
"More than 1,000 species of bacteria live in our guts, in a symbiotic population called the microbiota," says Gabriel Nunez, M.D., the U-M pathologist who led the research team. "These results show that these bacteria, also called commensals, compete with pathogens (disease-causing bacteria) in a previously unappreciated way - and that the pathogens use a specific set of genes to temporarily outcompete commensals before leaving the body. Understanding this gives us potential targets for prevention and treatment."
For instance, since the research shows that harmful bacteria compete with commensal bacteria for certain nutrients that they need to survive, selectively removing some nutrients and boosting others might help. So might a more targeted use of antibiotics when treating patients who are battling an E. coli infection.
Nunez and first author Nobuhiko Kamada, Ph.D., a postdoctoral fellow, made the findings by studying mice that they infected with C. rodentium - the rodent equivalent of harmful E. coli. The study included specially bred germ-free mice that lacked all the "good" gut bacteria that normal mice and humans harbor.
Both Nunez and Kamada are members of the U-M Medical School's Department of Pathology and the U-M Comprehensive Cancer Center, and the work fits into their broader investigations of how inflammation and immunity play a role in the body's response to cancer as well as infections.
Fittingly, Nunez holds the Paul H. de Kruif Professorship in Pathology, named for the U-M graduate who wrote Microbe Hunters, a pivotal 1926 book on the history of infectious disease research.
In the new paper, the team adds a new chapter to the understanding of how pathogenic bacteria gain a foothold in the gut - literally - by turning on virulence genes that allow them to attach to the cells that line the digestive tract.
This attaching-and-effacing activity, as it is called, allows the disease-causing bacteria to intimately adhere to the cells that line the gut, consume nutrients and reproduce, out-competing the natural gut bacteria. But this comfortable niche only lasts a few days or weeks, during which the host's gut gets more inflamed as the immune system responds to the insult. Diarrhea, sometimes containing blood that leaks from the gut lining, results.
And that, the researchers find, is when the pathogens stop expressing the virulence genes that allowed them to gain their upper hand. They unhitch from the gut lining, mixing in with the commensal bacteria in the open center (lumen) of the gut, and fighting for what food they can find.
While this return to competition means that some of them die, enough of them survive to be expelled in the feces. And if good sanitation systems aren't in place, the bacterial offspring have a good chance of finding a new host to take a toll on.
Better sanitation throughout the world can prevent infections in the first place, says Nunez. But when infection by pathogenic bacteria occurs, a better understanding of the way they interact with our native bacteria could eventually help save lives.
Nunez's team is working with the lab of U-M microbiologist and co-author Eric Martens, Ph.D., to screen different sugars that, if withheld or enhanced in the diet, might weaken the pathogens' effects. That could lead to a better understanding of how children and weak adults in developing nations should be fed while being treated for infection.
The University of Michigan has applied for patent protection, and is in the process of looking for commercialization partners to help bring the technology to market.
The research was supported by grants from the National Institutes of Health, CONACyT, CIHR, the Uehara Memorial Foundation, and the Crohn's and Colitis Foundation of America. Several specialized core research facilities at the U-M Medical School were used in the work, including the Germ-free Animal Core, the Microscopy and Image Analysis Laboratory, and the Center for Molecular Imaging.
Reference: Science Express - Regulated Virulence Controls the Ability of a Pathogen to Compete with the Gut Microbiota - Manuscript Number: science.1222195
University of Michigan Health System
Related Pathogenic Bacteria Current Events and Pathogenic Bacteria News Articles
Google glass meets organs-on-chips
Investigators from Brigham and Women's Hospital (BWH) have developed hardware and software to remotely monitor and control devices that mimic the human physiological system.
Autoimmune diseases gonna be defeated
An international team of scientists led by the Lomonosov Moscow State University group made a significant step in creating a new type of drug for treatment of autoimmune diseases, such as rheumatoid arthritis and Crohn's diseaase.
Simpler technique yields antibodies to a range of infectious agents
Researchers hope to develop vaccines, therapeutics and new diagnostic tests for a broad range of diseases.
Researchers identify most dangerous strains of often-deadly bacteria
A multi-disciplinary group of researchers at the University of Maryland School of Medicine (UM SOM) have for the first time determined the genetic makeup of various strains of E. coli, which every year kills hundreds of thousands of people around the world.
Molecular switch lets salmonella fight or evade immune system
Researchers at the University of Illinois at Chicago have discovered a molecular regulator that allows salmonella bacteria to switch from actively causing disease to lurking in a chronic but asymptomatic state called a biofilm.
Scientists discover that the immune system affects gut bacteria evolution
Our health is strongly dependent on the diversity of bacteria that inhabits our intestinal tract and on how the immune system tolerates it or responds to the pathogenic bacteria to prevent disease.
Scripps Florida team discovers compounds with potential to treat persistent tuberculosis
Tuberculosis has been infecting humans for several millennia, making it one of the most horribly successful diseases in history. Today, it is still a major killer, responsible for some 1.5 million deaths each year.
Decoding the microbial signature of aggressive form of breast cancer
Cancer is a result of normal cellular functions going wildly awry on a genetic level. That fact has been known for some time, but increasing evidence is showing that the human microbiome, the diverse population of microorganisms within every person, may play a key role in either setting the stage for cancer or even directly causing some forms of it.
Wastewater treatment plants not responsible for spreading antimicrobial resistance
In collaboration with colleagues from Aalborg University, Technical University of Denmark (DTU) researchers have studied genes from wastewater treatment plants that may help bacteria to develop antimicrobial resistance.
Bacteria in ancient flea may be ancestor of the Black Death
About 20 million years ago a single flea became entombed in amber with tiny bacteria attached to it, providing what researchers believe may be the oldest evidence on Earth of a dreaded and historic killer - an ancient strain of the bubonic plague.
More Pathogenic Bacteria Current Events and Pathogenic Bacteria News Articles