Microneedle array delivery of Yersinia pestis recapitulates bubonic plague

Sarah L. Price; Robert S. Oakes; Rodrigo J. Gonzalez; Camilla Edwards; Amanda Brady; Jennifer K. DeMarco; Ulrich H. von Andrian; Christopher M. Jewell; Matthew B. Lawrenz

iScience (Jan 2024)

Microneedle array delivery of Yersinia pestis recapitulates bubonic plague

Sarah L. Price,
Robert S. Oakes,
Rodrigo J. Gonzalez,
Camilla Edwards,
Amanda Brady,
Jennifer K. DeMarco,
Ulrich H. von Andrian,
Christopher M. Jewell,
Matthew B. Lawrenz

Affiliations

Sarah L. Price: Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA
Robert S. Oakes: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA; Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD 21201, USA
Rodrigo J. Gonzalez: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA; The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
Camilla Edwards: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA
Amanda Brady: Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA
Jennifer K. DeMarco: Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA
Ulrich H. von Andrian: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA; The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
Christopher M. Jewell: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA; Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD 21201, USA; Robert E. Fischell Institute for Biomedical Devices, College Park, MD 20742, USA; Department of Microbiology and Immunology, University of Maryland Medical School, Baltimore, MD 21201, USA; Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical School, Baltimore, MD 21201, USA
Matthew B. Lawrenz: Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA; Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 1
p. 108600

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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