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Microneedle array delivery of Yersinia pestis recapitulates bubonic plague
Sarah L Price1, Robert S Oakes2,3, Rodrigo J Gonzalez4,5
1Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Abstract:
Fleas transmit Yersinia pestis directly within the dermis of mammals to cause bubonic plague. Syringe-mediated inoculation is widely used to recapitulate bubonic plague and study Y. pestis pathogenesis. However, intradermal needle inoculation is tedious, error prone, and poses a significant safety risk for laboratorians. Microneedle arrays (MNAs) are micron-scale polymeric structures that deliver materials to the dermis, while minimizing the risk of needle sticks. We demonstrated that MNA inoculation is a viable strategy to recapitulate bubonic plague and study bacterial virulence by defining the parameters needed to establish a lethal infection in the mouse model and characterizing the course of infection using live-animal optical imaging. Using MNAs, we also demonstrated that Y. pestis must overcome calprotectin-mediated zinc restriction within the dermis and dermal delivery of an attenuated mutant has vaccine potential. Together, these data demonstrate that MNAs are a safe alternative to study Y. pestis pathogenesis in the laboratory.
Insights
Microneedle arrays (MNAs) offer a safer method for studying bubonic plague by enabling direct dermal inoculation of Yersinia pestis. This technique overcomes the risks associated with traditional needle injections, improving laboratory safety and research efficiency.
Area of Science:
- Microbiology
- Infectious Diseases
- Biotechnology
Background:
- Fleas transmit Yersinia pestis, the causative agent of bubonic plague, directly into mammalian dermis.
- Syringe-mediated intradermal inoculation is standard for Y. pestis research but poses risks to laboratory personnel.
Purpose of the Study:
- To evaluate microneedle arrays (MNAs) as a safe and effective alternative for Y. pestis dermal inoculation.
- To characterize Y. pestis pathogenesis and host-pathogen interactions using MNA delivery.
Main Methods:
- Development and application of MNA technology for controlled Y. pestis dermal delivery in a mouse model.
- Live-animal optical imaging to track infection progression.
- Assessment of Y. pestis interaction with host immune factors, specifically calprotectin-mediated zinc restriction.
Main Results:
- MNA inoculation successfully recapitulated lethal bubonic plague in mice.
- Defined parameters for establishing Y. pestis infection via MNA delivery.
- Demonstrated Y. pestis must overcome dermal zinc restriction and identified vaccine potential for attenuated mutants delivered via MNA.
Conclusions:
- Microneedle arrays provide a safe and viable alternative to syringe inoculation for studying Y. pestis pathogenesis.
- MNA technology facilitates research into bacterial virulence mechanisms and potential vaccine development.
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