Brucellosis infection cycle being examined

Brucellosis infection cycle being examined

New insights into how brucella infects cells could help fight off other diseases like tuberculosis and salmonella.

BRUCELLOSIS, Malta fever, Bang's disease, undulant fever — all are names for an understudied infectious disease that stalks animals and people worldwide.

Now, however, Washington State University microbiologist Jean Celli is uncovering some of the secrets of the brucella organism's success, adding to the emerging knowledge about how the rod-shaped bacteria spread inside the body and outwit the immune system.

Not only does brucellosis harm valuable livestock, but it can leave people chronically ill for years, said Celli, a recent hire at Washington State's Paul G. Allen School for Global Animal Health. Although the bacterium that causes the disease was isolated more than a century ago, "we're still in the early stages of understanding how it carries out infections inside the body," he said.

Brucellosis spreads from animals to people — mostly through ingesting unpasteurized milk and its byproducts or contact with infected animals' raw meat and secretions, according to the Centers for Disease Control & Prevention.

"It's stealthy, expensive to treat and hard to cure," Celli said. "We know how brucella gets transmitted from animals to humans. We know how it enters the host cell, but we still have a lot to learn about how it produces disease and how it's able to keep the immune system from destroying it."

Research on brucellosis is limited, in part, because the disease is no longer common in the U.S., said Guy Palmer, Regents professor and director of the Allen School. An aggressive livestock vaccination program, public health surveillance and milk pasteurization requirements have all lowered nationwide cases in people to fewer than 200 reported each year, he explained.

However, the pathogen is still out there. Worldwide, roughly a half-million people are infected annually, making it one of the most common zoonotic diseases on the planet, according to the World Health Organization.

That's why Celli's work on the bacteria is so important, Palmer said.

"In countries that don't have adequate animal disease programs, brucellosis is a big financial loss to families and farmers who depend on beef and dairy livestock for food," he explained. When people become infected, "it's a tough bug to get rid of. Antibiotics don't always work, and the disease can wax and wane for many years."


Persistent nature

In a full-blown brucellosis infection, animals deliver stillbirths and are left with damaged reproductive organs. People develop deep fatigue, aches, joint pain and a telltale fever that spikes and crashes in waves — hence one of brucellosis's other names, undulant fever.

Even with the standard four to six weeks of antibiotics, brucella bacteria can stubbornly persist. Symptoms may disappear, only to resurface many years later. That's because they are chronic boarders that hide in lymph nodes and then fan out to joints and organs in the bloodstream, where they hide once again.

"It is at this stage that we know the bacteria also replicate," Celli said.

What's more, the very immune cells that are supposed to engulf and destroy foreign intruders do engulf brucella but then instead provide the invaders with a place to hide and even transport them deep within the body, the announcement said.

"Immune cells are supposed to create an inhospitable environment for bacteria, but it's different with brucella, which use the immune cells to their advantage to carry out infection," said Celli, who, while working at the National Institutes of Health, published research on how the bacteria exploit normal immune defenses and spread.

As Celli and his colleagues discovered, once inside an immune cell, the bacteria seek refuge within the endoplasmic reticulum compartment, which provides protection. There, they replicate, eventually breaking out and infecting neighboring cells.

"The bacteria change the normal functioning of the host cell so that they can survive, proliferate and produce disease," Celli explained. "By injecting proteins into the host cells, the tiny bacteria band together and highjack the normal defense response. It's a fascinating cellular process. Our understanding of it could shed light on what goes on inside our bodies in response to other pathogens as well."

At Washington State, it's a cellular process that Celli will further probe.

"If we can figure out how the bacteria signal the host cell to create those compartments and what triggers the bacteria's release from those compartments, it could eventually lead to the development of drugs that block the infection process before the disease is induced," Celli said.

What's more, new insights could help fight off other diseases that highjack the immune system, such as tuberculosis and salmonella, he said.

Volume:85 Issue:40

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