Mechanics of bacterium's toxin being unraveled

May 21, 2002

SALT LAKE CITY -- Researchers are unraveling the mystery of what happens when a bacterium's toxin hits its cellular target. In an age of growing antibiotic resistance and a threat of bioterrorism, such knowledge may help to open new lines of treatment, says a microbiologist at the University of Illinois at Urbana-Champaign.

In a presentation today at the 102nd annual meeting of the American Society for Microbiology, Brenda A. Wilson described her basic research and recent findings involving Pasteurella multocida, a bacterium that once left her hospitalized and near death. The bacterium, she said, offers a window to view the mechanics of many toxin-mediated bacterial diseases, including anthrax, which left five people dead from acts of terrorism last year despite extensive treatment with antibiotics.

"A big problem now is antibiotic resistance, but we also need alternative strategies for attacking toxin-mediated disease after exposure to toxins," she said in an interview in advance of her talk. "Current strategies, such as vaccine therapy or treatment with antitoxins or other inhibitors, are focused on blocking a toxin from binding to cells. My studies consider that exposure has already occurred. Once the toxin is in and hits its target, what do we do? I want to understand what a toxin does after it hits the target."

Pasteurella multocida is a well-known pathogen in veterinary medicine. Its various strains affect domesticated and agricultural animals, leading usually to serious, and often deadly, respiratory infections. Contact with animals sometimes results in respiratory problems in humans, and skin infections can occur after being bitten by an animal. The bacterium is even part of the Komodo dragon's deadly bite.

Disease doesn't always occur, Wilson said, but a synergistic effect with another microorganism, such as Mycoplasma or Bordatella, often has serious consequences.

In 1997, Wilson discovered that the Pasteurella multocida toxin's target is a protein known as Gq, which regulates a variety of hormonal activities inside cells. "The role that Gq plays in a particular cell will determine what form the cellular damage takes when the toxin acts on it," she said.

Antiobiotics until recent years have killed many kinds of bacteria, but even as they die some bacteria still can release toxins into the body. In many cases, just one toxin can enter a cell and alter its structure or kill it. Once toxins are released, she said, "you reach a point of no return, where you have a toxin disease no longer treatable with antibiotics even if you have completely removed the bacterium from the body." In her talk, Wilson announced the construction of a tool "that allows us to visualize the pathway a toxin takes into a cell." Her unpublished technique utilizes a synthetic green-fluorescent protein attached to the toxin protein. The added green protein, when visualized with a fluoresence microscope, accompanies the toxin during invasion and entry into a cell.

The tool, she said, will allow researchers to test inhibitors or other blocking agents that might be developed to fight toxin-mediated infections.

Wilson also discussed new findings from the May 3 issue of Circulation Research, in which she and her Columbia University collaborators, Susan F. Steinberg and Abdelkarim Sabri, reported that the Pasteurella multocida toxin attacks cardiac cells in two distinct ways. They found that at low concentrations the bacterium causes cardiac hypertrophy, an indicator of heart disease in which cells proliferate and enlarge the organ. At higher toxin levels, heart cells become susceptible to rapid destruction by other damaging agents. The toxin, Wilson said, can now be used as a potent tool to study heart disease processes.

She also provided a brief overview of her progress studying the bacterium's toxic attack on skin and cells, particularly on the toxin's ability to completely block fat accumulation. She theorizes that what she is seeing may partially explain the "wasting syndrome" often observed in infected animals.
-end-


University of Illinois at Urbana-Champaign

Related Heart Disease Articles from Brightsurf:

Cellular pathway of genetic heart disease similar to neurodegenerative disease
Research on a genetic heart disease has uncovered a new and unexpected mechanism for heart failure.

Mechanism linking gum disease to heart disease, other inflammatory conditions discovered
The link between periodontal (gum) disease and other inflammatory conditions such as heart disease and diabetes has long been established, but the mechanism behind that association has, until now, remained a mystery.

New 'atlas' of human heart cells first step toward precision treatments for heart disease
Scientists have for the first time documented all of the different cell types and genes expressed in the healthy human heart, in research published in the journal Nature.

With a heavy heart: How men and women develop heart disease differently
A new study by researchers from McGill University has uncovered that minerals causing aortic heart valve blockage in men and women are different, a discovery that could change how heart disease is diagnosed and treated.

Heart-healthy diets are naturally low in dietary cholesterol and can help to reduce the risk of heart disease and stroke
Eating a heart-healthy dietary pattern rich in vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, vegetable oils and nuts, which is also limits salt, red and processed meats, refined-carbohydrates and added sugars, is relatively low in dietary cholesterol and supports healthy levels of artery-clogging LDL cholesterol.

Pacemakers can improve heart function in patients with chemotherapy-induced heart disease
Research has shown that treating chemotherapy-induced cardiomyopathy with commercially available cardiac resynchronization therapy (CRT) delivered through a surgically implanted defibrillator or pacemaker can significantly improve patient outcomes.

Arsenic in drinking water may change heart structure raising risk of heart disease
Drinking water that is contaminated with arsenic may lead to thickening of the heart's main pumping chamber in young adults, according to a new study by researchers at Columbia University Mailman School of Public Health.

New health calculator can help predict heart disease risk, estimate heart age
A new online health calculator can help people determine their risk of heart disease, as well as their heart age, accounting for sociodemographic factors such as ethnicity, sense of belonging and education, as well as health status and lifestyle behaviors.

Wide variation in rate of death between VA hospitals for patients with heart disease, heart failure
Death rates for veterans with ischemic heart disease and chronic heart failure varied widely across the Veterans Affairs (VA) health care system from 2010 to 2014, which could suggest differences in the quality of cardiovascular health care provided by VA medical centers.

Heart failure: The Alzheimer's disease of the heart?
Similar to how protein clumps build up in the brain in people with some neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, protein clumps appear to accumulate in the diseased hearts of mice and people with heart failure, according to a team led by Johns Hopkins University researchers.

Read More: Heart Disease News and Heart Disease Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.