B. Joseph Hinnebusch, Ph.D.

Chief, Plague Section 
Investigator

Xenopsylla cheopis flea infected with Yersinia pestis. The foregut of this flea is blocked by a Y. pestis biofilm, which is prerequisite for efficient transmission.

Description of Research Program

This laboratory studies mechanisms of Yersinia pestis transmission and pathogenicity. Yersinia pestis, the cause of bubonic and pneumonic plague in humans, is transmitted primarily by fleas and has been responsible for devastating pandemics throughout history, including the Black Death of fourteenth century Europe. Plague re-emerged in India and Africa during the 1990s and remains an international public health concern. The isolation of antibiotic resistant strains of Y. pestis and the potential use of Y. pestis by bioterrorists increases the urgency for better medical countermeasures against plague.

Infected rat lymph node (bubo) containing massive numbers of Yersinia pestis with associated necrosis, hemorrhage, and coagulation (H&E stained section, 200x).

One research goal is to identify and determine the function of Y. pestis genes that mediate transmission by fleas. Detailed understanding of the interaction with the insect vector may lead to novel strategies to interrupt the transmission cycle and may be applicable to other arthropod-borne agents. For example, determining the vector-specific antigens expressed on the Y. pestis surface as the bacteria exit the flea and enter the mammal may help in the design of new efficacious vaccines and diagnostics.

A second goal is to identify and determine the pathogenic mechanism of specific Y. pestis virulence factors and to characterize the host response to naturally acquired infection, using animal models that incorporate the natural flea-borne route of transmission. Genome-scale methods are available to study these mechanisms in both the insect vector and mammalian host model systems.

Major Areas of Research

• Molecular mechanisms of Yersinia pestis transmission by fleas
• Molecular mechanisms of plague pathogenesis and host response

Research Group Members

Clayton Jarrett, M.S., Microbiologist; Florent Sabbane, Ph.D., Visiting Fellow, 2002-present; David Erickson, Ph.D., Visiting Fellow, 2003-present; Nadine Lemaitre, M.D., Ph.D., Visiting Fellow, 2004-present.

Selected Recent Publications

Sebbane FD, Gardner D, Long B, Gowen B, Hinnebusch BJ. Kinetics of disease progression and host response in a rat model of bubonic plague. Am J Pathol. 2005. 166: 1427-1439.

Lorange EA, Race BL, Sebbane F, Hinnebusch BJ. Poor vector competence of fleas and the evolution of hypervirulence in Yersinia pestis. J Inf Dis. 2005. 191: 1907-1912.

Jarrett CO, Sebbane F, Adamovicz JJ, Andrews GP, Hinnebusch BJ. Flea-borne transmission model to evaluate vaccine efficacy against naturally acquired bubonic plague. Infect Immun. 2004. 72: 2052-2056.

Hinnebusch BJ, Rudolph AE, Cherepanov P, Dixon JE, Schwan TG, Forsberg A. Role of Yersinia murine toxin in survival of Yersinia pestis in the midgut of the flea vector. Science. 2002. 296: 733-735.

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