Research Interest: Pathogenesis of pneumonic plague
Ph.D.: Medical College of Wisconsin
Postdoctoral: University of North Carolina at Chapel Hill
Our research interests focus on pulmonary infection with highly virulent bacterial pathogens. Specifically, our laboratory is interested in understanding the pathogenesis of pulmonary infection with Yersinia pestis. Yersinia pestis is the causative agent of plague and one of the deadliest pathogens known to man. Plague remains an enzootic infection on every populated continent except Australia, and its pandemic capacity and potential to cause significant morbidity and mortality is well-established. Y. pestis is responsible for at least three major pandemics in recorded history, including the Black Death of the Middle Ages. Primary pneumonic plague is the most severe manifestation of plague and is highly transmissible via the respiratory route. The time from inhalation exposure to death in humans is typically between four and seven days. Further, if antibiotics are not administered within 24 hours after the onset of symptoms, pneumonic plague is nearly 100% fatal. A lack of understanding of the bacterial and host factors contributing to the progression of pneumonic plague is a significant barrier to the development of advanced treatment options.
Our laboratory uses a murine infection model of pneumonic plague that allows for the detailed characterization of disease progression in a natural Y. pestis host, and closely mirrors disease as it manifests in humans. The progression of pneumonic plague is biphasic, with an initial “pre-inflammatory” phase in the lung highlighted by a lack of disease symptoms or detectable host responses. After 36-48 hours, there is an abrupt switch into a “pro-inflammatory” phase of disease characterized by the rapid onset of symptoms, induction of pro-inflammatory cytokines, and the dramatic accumulation of immune infiltrate in the airways. The work in our laboratory seeks to characterize the host/pathogen interactions responsible for the biphasic progression of disease. Additionally, we are interested in defining the mechanisms and effects of inflammation-mediated pulmonary damage that occur during pulmonary infection. Our laboratory uses molecular tools to dissect the pathogenesis of pneumonic plague in detail by focusing on four primary areas: 1. Identification of bacterial factors that contribute to infection; 2. Characterizing direct host/pathogen interactions in vivo during infection; 3. Characterizing host responses to pulmonary infection; 4. Identifying novel therapeutic approaches to treating late-stage pneumonic plague.
- Pechous RD, Goldman WE. Illuminating Targets of Bacterial Secretion. Hogan DA, ed. PLoS Pathogens. 2015;11(8):e1004981. doi:10.1371/journal.ppat.1004981.
- Sivaraman V, Pechous RD, Stasulli NM, Eichelberger KR, Miao EA, Goldman WE. Yersinia pestis Activates Both IL-1β and IL-1 Receptor Antagonist to Modulate Lung Inflammation during Pneumonic Plague. Weiss D, ed. PLoS Pathogens. 2015;11(3):e1004688. doi:10.1371/journal.ppat.1004688.
- Pechous RD, Broberg CA, Stasulli NM, Miller VL, Goldman WE. In Vivo Transcriptional Profiling of Yersinia pestis Reveals a Novel Bacterial Mediator of Pulmonary Inflammation. mBio. 2015;6(1):e02302-14. doi:10.1128/mBio.02302-14.
- Pechous RD, Sivaraman V, Price PA, Stasulli NM, Goldman WE. Early Host Cell Targets of Yersinia pestis during Primary Pneumonic Plague. Kazmierczak BI, ed. PLoS Pathogens. 2013;9(10):e1003679. doi:10.1371/journal.ppat.1003679.