This season's tornado outbreak in the U.S. left some unusual casualties in its wake. At least three people have reportedly died from a virulent fungal infection and several more remain infected following the storms that struck Missouri last month.

Such severe fungal infections are rare but can be fatal if allowed to spread throughout the body—especially for people with compromised immune systems. A fungus's severity had been thought to be a factor of its type or method of spreading. But new research suggests that there is one key determinant in how deadly a fungal infection is going to be: spore size.

The pathogenic species of Mucor circinelloides can produce spores that are about 20 microns long—more than five times the size of other spores from the same species. Although smaller spores are more adept at lodging in vulnerable tissue, such as the lung, these supersize spores are less vulnerable to attack from the body's immune systems. In particular, they seem to be too large to fall prey to macrophages, which are usually charged with consuming and killing harmful invaders. Instead, these large fungal spores overpower the macrophages and kill them, making the body more vulnerable to further infection.

To better understand why large spores are so dangerous, researchers recently engineered small spores of M. circinelloides to go into overdrive growth in the lab. The spores started behaving more like the larger breed, skipping a middle growth phase and taking off into explosive growth. The hope is that getting a handle on that accelerating process will help scientists "to find a way to arrest them in the smaller stage before they grow into more virulent, larger spores," Soo Chan Lee, of the Department of Molecular Genetics and Microbiology at Duke University Medical Center, and co-author of the new study, said in a prepared statement.

The findings, published online June 16 in PLoS Pathogens, reveal the insidious power of "cell gigantism, which lets pathogenic fungi establish infection in the hosts" before the jumbo-size spores take over, Joseph Heitman, chair of the same department at Duke and co-author of the study, said in a prepared statement.

Severe fungal infections, such as those seen in Missouri's victims, seem to be more prevalent among people who have preexisting conditions, such as diabetes. "Having a high blood-glucose level is immunosuppressive and predisposes diabetic patients to difficult-to-manage fungal infections," Heitman said. In the new research, the team used a diabetic mouse model. And early diagnosis and treatment is not a guarantee for survival. A 2009 Journal of Global Infectious Diseases case study described a 48 year-old diabetic man who was promptly diagnosed with—treated for—the fungal infection but still succumbed to it.

In the Missouri victims, spores likely settled in tornado-related wounds, leading to zygomycosis, a fungal infection that has spread to the brain, lungs or sinuses. "We could visibly see mold in the wounds," Uwe Schmidt, who specializes in infectious diseases at the Freeman Health System, told the Springfield News-Leader last week. If the infection is limited to a small area, infected tissue can be amputated, but a wound combined with a compromised immune system provides the fungus with a clear path to more crucial tissues and internal organs. About half of people who contract an M. circinelloides infection die from it, but its prevalence in the U.S. is currently unknown. 

Image courtesy of: Valerie Knowlton/NC State University/Joseph Heitman/Soo Chan Lee/Duke University Medical Center