Sean Crosson, a Professor Rudolph Hugh Endowed Chair at Michigan State University’s Department of Microbiology, Genetics, and Immunology, has been awarded a $2.4 million grant from the National Institutes of Health to study the cause of Bang’s disease: Brucella abortus.

Known as Bang’s disease or undulant fever, brucellosis is a highly contagious condition affecting cattle, bison, and swine, leading to infertility, lameness, and loss of young. It can also infect humans, presenting serious health risks. Alarmingly, Brucella abortus is becoming increasingly antibiotic-resistant, making treatment more challenging.

While the U.S. Department of Agriculture’s eradication efforts since the 1950s have largely controlled the disease in domestic livestock, wild elk and bison in the Yellowstone area still carry the bacteria, creating a risk of transmission to grazing livestock. Globally, the disease poses a greater threat in resource-limited regions where livestock and humans live in close proximity.

“Worldwide, it’s a major burden on agriculture and human health, as well as economic productivity in regions where livestock are critical to livelihoods,” Crosson explained. “Its impact on global health and agriculture is significant.”

Pioneering Vaccine Research

Crosson’s NIH-funded project, titled “Regulation of the Brucella abortus General Stress Response,” aims to explore the genetic mechanisms that enable Brucella to survive within its host. This foundational research could pave the way for vaccines targeting wildlife populations, such as elk and bison, which remain reservoirs for the disease.

“We have immune cells called phagocytes that engulf and destroy foreign invaders,” Crosson explained. The term “phagocyte” comes from the Greek words for “to devour” (phagein) and “cell” (cyte).

However, Brucella has developed sophisticated strategies to evade this defense mechanism. When engulfed by phagocytes, microbes are subjected to acidic and chemical stress that typically halts their growth. Crosson’s research focuses on Brucella’s ability to detect and adapt to these environmental changes through what’s known as the general stress response.

“This microbe has a toolkit that allows it to secrete proteins that trick the host cell into isolating it in a neutral compartment, where it can replicate,” Crosson said. “Understanding this stress response is key to developing better vaccines.”

Key Research Goals

Crosson’s research targets three specific mechanisms that enable Brucella to evade host defenses:

1. Photosensor Protein
   Brucella uses a photosensor protein to detect environmental changes. Knocking out the gene for this protein eliminates Brucella’s ability to infect animals, highlighting its potential as a vaccine target.

2. EipB Protein and Cell Envelope Stability
   The second focus is a protein called EipB, which helps maintain the structural integrity of Brucella’s cell envelope—a barrier protecting the bacterium’s inner contents.

   “We’ve determined the structure of EipB using X-ray diffraction, but we’re still exploring its precise role in stabilizing the envelope under stress,” Crosson explained.

3. Noncoding RNAs GsrN1 and GsrN2
   Finally, Crosson’s team is investigating two noncoding RNAs, GsrN1 and GsrN2, which appear to play a role in Brucella’s gene regulation. While deleting either RNA has minimal impact, removing both reduces the bacterium’s ability to colonize the spleen in mouse models.

   “We want to understand the mechanisms behind these RNAs and their contributions to Brucella’s stress response,” Crosson said.

By unraveling these pathways, Crosson hopes to provide the groundwork for developing vaccines that prevent Brucellainfections in wildlife and protect livestock from potential outbreaks. “This work is vital for human health, agriculture, and global economic stability,” he concluded.