Standardized Method for Aerosol Challenge of Rodents with Yersinia pestis for Modeling Primary Pneumonic Plague

Abstract

Primary pneumonic plague occurs when Yersinia pestis is inhaled into the lower respiratory tract where it invades the alveoli and grows. Rapid bacterial growth eventually elicits a neutrophilic inflammatory response that is ineffective and damaging, leading to accelerated progression of disease. In the laboratory, modeling of primary pneumonic plague can be accomplished by instillation of bacterial culture in the nares of anesthetized mice and rats. Although primary pneumonic plague can develop from this method, variability in dosing and side effects of anesthesia can complicate data interpretation. In contrast, aerosol challenge models allow for well-controlled studies of pneumonic plague with minimal experimental bias and unwanted side effects. For these reasons, antibiotic testing and the licensing of new treatments depend on efficacy data generated from aerosol delivery of Y. pestis in order to more accurately model transmission and the early stages of human pneumonic plague. In order to meet this need, we have extensively characterized pneumonic plague in mice and rats challenged by nose-only exposure to Yersinia pestis. With this approach, simultaneous challenge of large cohorts of animals, gently restrained and not anesthetized, assures safe, well-controlled, unbiased, and uniform infection. In this chapter, we present a standardized method for reproducible aerosol delivery of wild-type Y. pestis to rodents for experimental models of primary pneumonic plague.