Jean Celli, WSU microbiologist
WSU microbiologist Jean Celli probes the secrets of how brucella bacteria spread inside the body. (Photo by Shelly Hanks, WSU Photo Services)
PULLMAN – Brucellosis, Malta fever, Bang’s disease, undulant fever – all names for one infectious disease that stalks animals and humans worldwide, and yet it’s been understudied.

But that may be about to change.

Washington State University microbiologist Jean Celli is uncovering some of the secrets of brucella’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 WSU’s Paul G. Allen School for Global Animal Health. And though 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.

Cell infected with brucella
Celli infected this host cell with just 1-2 brucella, in red, and took this photo 72 hours later. Note how much the bacteria have replicated.

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 and Prevention.

“It’s stealthy, expensive to treat and hard to cure,” said Celli. “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.”

Magnify research at WSU

Research on brucellosis is limited, in part, because the disease is no longer common in the United States, 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 humans to less than 200 reported each year, he explained.

But the pathogen is still out there, doing its dirty work. From Asia and Africa to Mexico and Eastern Europe — roughly a half-million humans 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, said Palmer.

“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. And when humans 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.”

Bug’s persistent nature

In a full-blown brucellosis infection, animals deliver stillbirths and are left with damaged reproductive organs. Humans 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.

“The disease rarely kills anybody, but it often makes a patient wish he were dead” wrote TIME magazine in 1943, before the U.S. government required commercial pasteurization of milk and before the development of antibiotic treatments.

But even with the standard 4-6 weeks of antibiotics, brucella bacteria can stubbornly persist. Symptoms may disappear, only to resurface many years later. That’s because they are the ultimate chronic boarders, hiding in lymph nodes and then fanning 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,” said Celli.

What’s more, the very warrior cells that are supposed to engulf and destroy foreign intruders instead do something very different: Immune cells engulf the Brucella all right, but then they provide the invaders a place to hide and even transport them deep within the body.

Outwits the defense

“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 (See: Cell Host & Microbe, Jan. 19, 2012: http://www.sciencedirect.com/science/article/pii/S1931312811003994).

As Celli and his colleagues discovered, once inside an immune cell, the bacteria seek refuge within a compartment called the endoplasmic reticulum that 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,” explained Celli. “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 WSU, it’s a cellular process that Celli will further probe.

Mother and baby cow
Calves in the U.S. are tattooed on the ear for proof that they were vaccinated.

“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,” said Celli.

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

When dairy isn’t king

In Washington state, no cases of brucellosis have been reported in cattle since it was eradicated in 1988, according to the state’s department of health. Nationwide, calves are tattooed on the ear to show proof they’ve been vaccinated.

Consuming raw dairy products in other countries is the biggest reason American citizens continue to get infected, according to the CDC. Heat from the pasteurization process destroys potentially harmful microbes. “While it is possible to get foodborne illnesses from many different foods, raw milk is one of the riskiest of all.”