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
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.
