Microbiologists at the University of Louisville study Yersinia pestis, the bacteria that causes bubonic plague, however, because it has the potential to be used as a bioweapon and it provides knowledge that may help defeat other bacteria. Through this work, they have made an important discovery about a molecule secreted by Y. pestis and other bacteria that helps defeat the host’s immune defenses, allowing the bacteria to infect its hosts.

Sarah Price, a doctoral student researcher, and her mentor, Matthew Lawrenz, associate professor of microbiology and immunology, have found that yersiniabactin, a small molecule secreted by Y. pestis, gathers zinc, a necessary element for bacterial replication. This discovery may have implications in other infections as well since bacteria causing pneumonia, sepsis and other illnesses also are known to release yersiniabactin.

“While yersiniabactin’s role in iron acquisition has been well known for over 30 years, we were surprised to see its significant impact on zinc acquisition during Y. pestis infection,” Price said “This is very exciting because it helps us understand how Y. pestis and other bacteria acquire nutrients that allow them to cause disease.”

Invading bacteria as well as the hosts they infect all require iron, zinc and other metals in order to grow. The host’s immune system employs a strategy called nutritional immunity to protect against these bacterial infections, sealing the metals away from the bacteria.

It has been known for many years that yersiniabactin defeats this defense by stealing away iron and delivering it into the bacterial cells. Price and Lawrenz have discovered that the molecule also is involved in securing zinc and perhaps even other metals to assist Y. pestis infection.

Yersiniabactin also is used by Escherichia coli, which causes a multitude of infections such as intestinal illness and kidney infections, and Klebsiella pneumoniae, which causes pneumonia and sepsis. These more common diseases can be life-threatening and multidrug-resistant infections. The new understanding may lead to additional strategies for controlling infection by all of these bacteria.

An article describing the research published Oct. 29 in  provides details about how the researchers determined that yersiniabactin was responsible for the collection of not only iron, but zinc. Price is first author on the publication, “.” Lawrenz is senior author and researchers from the University of Kentucky, Washington State University and the University of Illinois also contributed to these studies.

“With this understanding of the broader role of yersiniabactin in plague infection, we can explore further to understand its role in enabling other bacteria to infect a human or other host,” Lawrenz said. “If this mechanism holds true across these bacteria, it may be possible to develop a drug or vaccine that could inhibit yersiniabactin’s effectiveness, thus preventing all of these infections.”

Bubonic plague most often is transmitted to humans through the bite of an infected flea, usually carried by a rodent. By not handling animal carcasses, preventing flea bites and avoiding contact with bodily fluids of those infected, the spread of bubonic plague is largely controlled. However, since human-to-human transmission is possible, mortality from an infection ranges from 30-to-90% and no vaccine is available to prevent the infection, it remains an important pathogen for research. In addition, Y. pestis, has the potential for weaponization and is considered a bioterrorism threat.

Lawrenz, Price and their colleagues conduct research within the , which focuses on the development of prevention and treatment strategies for infectious diseases and other harmful pathogens. Its researchers utilize the Regional Biocontainment Laboratory, a member of the National Institute of Allergy and Infectious Diseases network of 12 regional and 2 national biocontainment laboratories for studying infectious agents. The lab includes Biosafety Level 3 facilities built to the most exacting federal safety and security standards to protect researchers and the public from exposure to the pathogens being investigated. 

The center’s researchers were called upon in early 2020 to develop tests and prevention and treatment strategies against SARS-CoV-2, the virus that causes COVID-19. This work continues.

The students, led by junior applied geography (environmental analysis track) major and Grawemeyer Scholar Sam Kessler, invented the tool during a service project with Metropolitan Sewer District, Bernheim Forest and The Nature Conservancy. They volunteered to help monitor, clean up and restore streams in Louisville, including testing them for E.coli bacteria, which is found in biological waste and can sometimes cause disease. 

But, the team would have to consistently travel to each site — 10 sites across three different watersheds — at least five times per month to keep pace with the minimum testing required by the Environmental Protection Agency and Kentucky Department for Environmental Protection.

“With our class schedules, going to each of those sites multiple times per month wasn’t going to work for very long,” Kessler said. “We were traveling to some of these sites four times per week in between classes – Beargrass Creek, Bernheim Forest and all over. We needed something more efficient.”

To solve that problem, Kessler said, they invented a now patent-pending tool made from PVC pipe containing a special type of sediment material in mesh bags that can be left in the stream and read just once per month. Kessler believes their tool could dramatically improve the time and cost efficiency of testing.

“This is set-and-forget. You can leave it in the stream or river all month and test once instead of making at least five different trips,” he said. “And, because it’s in the stream all month instead of the isolated tests we currently do, you get more insightful results from a cumulative sample. This research could significantly improve the way we sample water for E.coli.”

Current testing only measures the levels of E.coli at the time of the test, not the days in between tests, Kessler said. For example, if a test on Monday shows no E.coli, the tester would have no way of knowing the stream was polluted the next day. Because the students’ tool can be left in the water all month, he said the result is a more comprehensive, cumulative sample.

“Understanding what makes safe, clean waterways is complex,” said Erin Wagoner, Environmental Partnerships Liaison for Louisville MSD. “From all the ways that land draining to a stream is used, to the chemical composition of the water in the stream, making these connections to improve the health of our waterways is a challenge. Creating a plan and developing a tool to make this process more efficient removes barriers to diagnosing the problems we are all trying to solve.”

While the tool has been tested only with E.coli so far, Kessler sees other potential applications. For example, he is interested in investigating whether it could be used to screen for SARS-CoV-2 by placing the device in wastewater.

“During COVID-19 specifically, limiting the amount of time human personnel are testing in the field is a smart thing to do,” Kessler said. “Maybe this could help.”