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Standardized Method for Aerosol Challenge of Rodents with Yersinia pestis for Modeling Primary Pneumonic Plague
Paul E Anderson1,2, Rachel M Olson1,2, Joshua L Willix1,2
1Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.
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.
Insights
A new standardized aerosol challenge method provides a reproducible model for studying pneumonic plague (caused by Yersinia pestis) in rodents. This approach ensures uniform infection for reliable antibiotic testing and new treatment development.
Area of Science:
- Microbiology
- Infectious Diseases
- Animal Models
Background:
- Primary pneumonic plague results from inhaled Yersinia pestis, leading to rapid bacterial growth and damaging inflammation.
- Current rodent models using intranasal instillation of Yersinia pestis suffer from variability and anesthesia side effects, complicating data interpretation.
- Well-controlled aerosol challenge models are crucial for accurate efficacy data in antibiotic testing and new treatment licensing for pneumonic plague.
Purpose of the Study:
- To present a standardized, reproducible method for aerosol delivery of Yersinia pestis to rodents for experimental models of primary pneumonic plague.
- To establish a reliable method for studying pneumonic plague that minimizes experimental bias and unwanted side effects.
- To facilitate the development and licensing of new treatments for pneumonic plague through improved animal modeling.
Main Methods:
- Development and characterization of a standardized nose-only aerosol challenge system for Yersinia pestis in mice and rats.
- Utilizing gentle restraint without anesthesia to challenge large cohorts of animals simultaneously.
- Ensuring uniform, well-controlled, and unbiased infection through precise aerosol delivery of wild-type Yersinia pestis.
Main Results:
- The described aerosol challenge method allows for simultaneous infection of large animal cohorts.
- The method ensures safe, well-controlled, unbiased, and uniform Yersinia pestis infection in rodents.
- This approach provides reproducible data crucial for evaluating antibiotic efficacy and developing new pneumonic plague treatments.
Conclusions:
- A standardized aerosol challenge method offers a reliable and reproducible model for primary pneumonic plague in rodents.
- This improved model is essential for generating accurate efficacy data for antibiotic testing and new therapeutic development.
- The method supports the accurate modeling of Yersinia pestis transmission and early-stage pneumonic plague in humans.
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