B. Joseph Hinnebusch, Ph.D.

Chief, Plague Section

Major Areas of Research

  • Interactions between the bacterium Yersinia pestis and its flea vectors 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

Program Description

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.





Xenopsylla cheopis flea infected with Yersinia pestis

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.

Credit
NIAID

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.

Credit:
NIAID

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.

Biography

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.

Selected Publications

Bland DM, Miarinjara A, Bosio CF, Calarco J, Hinnebusch BJ (2021) Acquisition of Yersinia murine toxin enabled Yersinia pestis to expand the range of mammalian hosts that sustain flea-borne plague. PLoS Pathogens 17(10): e1009995.

Bosio CF, Jarrett CO, Scott DP, Fintzi J, Hinnebusch BJ (2020) Comparison of the transmission efficiency and plague progression dynamics associated with two mechanisms by which fleas transmit Yersinia pestis. PLoS Pathogens 16(12):e1009092.

Shannon JG, Bosio CF, Hinnebusch BJ (2015) Dermal neutrophil, macrophage and dendritic cell responses to Yersinia pestis transmitted by fleas. PLoS Pathogens 11(3): e1004734.

Hinnebusch BJ, Jarrett CO, Bland DM (2017) “Fleaing” the plague: adaptations of Yersinia pestis to its insect vector that lead to transmission. Annu Rev Microbiol  71:215-232.

Chouikha I, Hinnebusch BJ (2014) Silencing urease: a key evolutionary step that facilitated the adaptation of Yersinia pestis to the flea-borne transmission route. Proc Natl Acad Sci USA 111:18709-18714

Sun YC, Jarrett CO, Bosio CF, Hinnebusch BJ (2014) Retracing the evolutionary path that led to flea-borne transmission of Yersinia pestis.  Cell Host Microbe 15:578-586

Visit PubMed to view a complete publication listing.

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