Characterization of the pigmentation locus in Yersinia pestis pathogenesis of pneumonic plague

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The extreme virulence of Yersinia pestis in all three forms of plague disease is attributed to its multiple virulence factors. Y. pestis pathogenesis research often focuses on characterization of these factors to better understand their regulation and mechanisms, in hopes of identifying potential targets useful for development of therapeutic and preventative options. Concern regarding a potential outbreak of Y. pestis disease in the form of pneumonic plague has led to heightened focus on elucidating the pathogenesis of this specific form of disease. In the studies presented here, we describe our discovery of the pigmentation (pgm) locus as containing one or multiple virulence factors necessary for the development of pneumonic plague. Pgm-deficient strains are commonly used for plague pathogenesis research due to its exclusion from select agent restrictions. However, our results have demonstrated its inapplicability as a model for pneumonic plague research as pgm-deficient strains are unable to cause respiratory disease. Further characterization of the siderophore-producing yersiniabactin (Ybt) system located in the pgm locus identified the Ybt siderophore as playing an essential role in bacterial growth within the lungs as well as potential immunomodulation of the host response. Additional studies to better understand the exact mechanism behind the effects of Ybt are needed to determine whether knowledge of this virulence factor can be used to our advantage in treatment and prevention.