Major Areas of Research
- Interactions between the bacterium Yersinia pestis and its rat-flea vector Xenopsylla cheopis that lead to transmission
- Mechanisms of Y. pestis pathogenicity and immune evasion
- Aspects of the flea-bacteria-host transmission interface that influence nascent infection and immunity
- Characterization of a protective immune response to plague; new plague vaccines and diagnostics
Yersinia pestis, the bacterial agent of bubonic and pneumonic plague, is one of the most virulent human bacterial pathogens and is well known historically for its ability to cause devastating pandemics. Plague remains an international public health concern and periodically re-emerges in the form of sudden large outbreaks. The emergence of antibiotic-resistant strains of Y. pestis and the potential use of Y. pestis as a biological weapon exemplify the need for better medical countermeasures against plague.
Figure 1: Xenopsylla cheopis flea infected with Yersinia pestis, shown as a dark mass. The foregut of this flea is blocked by a Y. pestis biofilm, which is a prerequisite for efficient transmission.
Research in the group focuses on the genetic and molecular processes of plague transmission, infection, and immunity. Studies apply modern molecular biology, genomics, and immunology tools to established flea and rodent infection models. One goal is to identify and determine the function of Y. pestis genes that mediate transmission by fleas. Detailed understanding of this interaction may lead to novel strategies to interrupt the transmission cycle. For example, determining the antigens expressed on the Y. pestis surface as the bacteria exit the flea and enter the mammal may help in the design of new vaccines and diagnostics.
Plague is a highly fulminant disease that rapidly leads to life-threatening sepsis. In vivo gene expression and immunologic analyses by this group indicate that the severity of disease depends on several Y. pestis virulence factors that thwart the mammalian innate immune response. This group is interested in understanding the detailed function of these factors and determining their specific targets and mechanisms. The group uses the natural flea-borne transmission route and systems to examine the intradermal flea-bacteria-host transmission interface. This enables scientists to take into account the effects of vector saliva and other factors specific to the microenvironment of the flea-bite site. The group also uses its animal model systems to identify and evaluate new Y. pestis antigens for use in plague vaccines and diagnostics and to characterize the host response to naturally acquired infection.
Dr. Hinnebusch received his Ph.D. in microbiology in 1991 from the University of Texas Health Science Center at San Antonio, studying the molecular structure and replication of linear plasmids of Borrelia burgdorferi, the bacterial agent of Lyme disease. He joined Rocky Mountain Laboratories as a postdoctoral fellow in 1992, where he developed model systems to study the transmission of Yersinia pestis, the bacterial agent of bubonic and pneumonic plague. He advanced to a tenure-track position in 2001. From 2002 to 2006, he was the recipient of a New Scholar Award in Global Infectious Diseases from the Ellison Medical Foundation.
L to R: Aaron Hasenkrug, Jeff Shannon, Justin Spinner, Iman Chouikha, Clay Jarrett, Chris Bosio, Joe Hinnebusch
Sun YC, Koumoutsi A, Jarrett C, Lawrence K, Gherardini FC, Darby C, Hinnebusch BJ. Differential control of Yersinia pestisbiofilm formation in vitro and in the flea veactor by two c-di-GMP diguanylate cyclases. PLoS One. 2011 Apr 29;6(4):e19267.
Sebbane F, Jarrett C, Gardner D, Long D, Hinnebusch BJ. Role of the Yersinia pestis yersinibactin iron acquisition system in the incidence of flea-borne plague. PLoS One. 2010 Dec 17;5(12):e14379.
Comer JE, Sturdevant DE, Carmody AB, Virtaneva K, Gardner D, Long D, Rosenke R, Porcella SF, Hinnebusch BJ.Transcriptomic and innate immune responses to Yersinia pestis in the lymph node during bubonic plague. Infect Immun. 2010 Dec;78(12):5086-98.
Vadyvaloo V, Jarrett C, Sturdevant DE, Sebbane F, Hinnebusch BJ. Transit through the flea vector induces a pretransmission innate immunity resistance phenotype in Yersinia pestis. PLoS Pathog. 2010 Feb 26;6(2):e10000783.
Sebbane F, Jarrett C, Gardner D, Long D, Hinnebusch BJ. The Yersinia pestis caf1M1A1 fimbrial capsule operon promotes transmission by flea bite in a mouse model of bubonic plague. Infect Immun. 2009 Mar;77(3):1222-9.