HJAR Jul/Aug 2019

Healthcare Journal of ARKANSAS I  JUL / AUG 2019 45 For weekly eNews updates and to read the journal online, visit HealthcareJournalAR.com knowledge and competency assessments, con- fidence surveys, virtual simulation, married-state preceptorship, and monthly live sessions with other residents, in addition to other learning opportunities.” Each participant also develops a special project. UAMS Lab’sWork on Plague Published in Infection and Immunity Roger D. Pechous, PhD, studies the bacte- ria that caused the infamous black death of the Middle Ages, shedding light on something old to potentially protect against something new— bioterrorism. The University of Arkansas for Medi- cal Sciences (UAMS) researcher’s latest work has been published in Infection and Immunity. Pechous is an assistant professor in the Depart- ment of Microbiology and Immunology in the UAMS College of Medicine. The article, titled “Modeling Pneumonic Plague in Human Preci- sion-cut Lung Slices Highlights a Role for the Plas- minogen Activating Protease in Facilitating Type 3 Secretion,” has been published online in advance of the August print edition of the journal. The bacterium is called Yersinia pestis. Pechous and Srijon Banerjee, a postdoctoral fellow in Pechous’ lab, study pneumonic plague, the severe lung infection caused by Yersinia pestisas it spreads from human to human through inha- lation. The World Health Organization (WHO) classifies pneumonic plague among the world’s deadliest infectious diseases. When the bacte- rium is spread by fleas, it is known as bubonic plague. Plague in the bloodstream is called sep- ticemic plague. “Y. pestis was responsible for three major pan- demics in recorded history and continues to be a potential threat worldwide, primarily due to concerns of its release as a weapon of bioter- ror,” Pechous said. “Human-to-human transmis- sion of plague occurs via the lungs, and is almost always lethal in the absence of timely treatment.” Banerjee said death from pneumonic plague typical occurs in four to seven days. If antibiotics are not administered within 24 hours of symp- tom development, it is nearly 100 percent fatal. It is one of the deadliest bacteria known to man. “What was unique about this study was its use of real human donor lung tissue, prepared to maintain realistic lung function in the labora- tory setting,” Banerjee said. “This allowed us to observe the way Y. pestis would behave in a living human lung and see what makes it so successful at overwhelming its human host.” Human lung tissue is cut into slices for the experiments in the Lung Cell Biology Labora- tory at the Arkansas Children’s Research Insti- tute by coauthor Richard C. Kurten, PhD, a pro- fessor of physiology & biophysics and pediatrics at UAMS. Kurten routinely acquires lungs from organ transplant donors and processes them for use in research in his laboratory and those of col- laborators at UAMS and across the country. From watching the behavior of Y. pestis in the lung slices in the lab, the researchers were able to pinpoint exactly how the bacteria quickly gains the upper hand. “We show that Y. pestis hones in on a key cell type and delivers key proteins that interfere with its ability to control infection and initiate an immune response,” Pechous said. “We identify a protein on the surface of Y. pestis that is critical for directing Y. pestis to specifically target this cell type to establish infection.” “All of this happens quickly,” Banerjee said. “By the time other signals alert the immune sys- tem to the severity of the infection, it’s too late. Ultimately, your own immune response is what ends up compromising lung function and lead- ing to death.” Pechous earned a doctorate from the Medical College of Wisconsin and completed postdoc- toral training at the University of North Carolina at Chapel Hill. He has been studying bacterial infec- tion since 2001. Banerjee earned a PhD from the University of Calcutta in India. The Pechous lab is another successful example from the UAMS Center for Microbial Pathogen- esis and Host Inflammatory Responses, directed by Mark Smeltzer, PhD. The center has earned $21 million in funding through the NIH’s Centers of Biomedical Research Excellence (COBRE) pro- gram, which aims to provide funding and mentor- ing to researchers who are early in their careers. Its participants are studying viruses, malaria, cancer, Lyme disease, and chlamydial infection. Pechous’ work is funded by the center and a grant from the NIH National Institute of Allergy and Infectious Diseases. UAMS has six COBRE centers, which are launch- ing new scientific careers, attracting top talent and creating concentrations of expertise on top- ics like neuroscience, cancer therapy, childhood obesity prevention, and pediatrics. In order to study Y. pestis at UAMS, the Pechous lab uses strict containment facilities and security procedures. n Srijon Banerjee, fellow, and Roger D. Pechous, PhD