Shift from primary #pneumonic to secondary #septicemic #plague by decreasing the volume of intranasal challenge with #Yersinia pestis in the murine model (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestis in the murine model

Rachel M. Olson , Deborah M. Anderson

Published: May 23, 2019 / DOI: https://doi.org/10.1371/journal.pone.0217440

 

Abstract

Yersinia pestis is the causative agent of pneumonic plague, a disease involving uncontrolled bacterial growth and host immunopathology. Secondary septicemic plague commonly occurs as a consequence of the host inflammatory response that causes vasodilation and vascular leakage, which facilitates systemic spread of the bacteria and the colonization of secondary tissues. The mortality rates of pneumonic and septicemic plague are high even when antibiotics are administered. In this work, we show that primary pneumonic or secondary septicemic plague can be preferentially modeled in mice by varying the volume used for intranasal delivery of Y. pestis. Low volume intranasal challenge (10μL) of wild type Y. pestis resulted in a high frequency of lethal secondary septicemic plague, with a low degree of primary lung infection and rapid development of sepsis. In contrast, high volume intranasal challenge (30μL) yielded uniform early lung infection and primary disease and a significant increase in lethality. In a commonly used BSL2 model, high volume challenge with Y. pestis lacking the pigmentation locus (pgm-) gave 105-fold greater deposition compared to low volume challenge, yet moribund mice did not develop severe lung disease and there was no detectable difference in lethality. These data indicate the primary cause of death of mice in the BSL2 model is sepsis regardless of intranasal dosing method. Overall, these findings allow for the preferential modeling of pneumonic or septicemic plague by intranasal dosing of mice with Y. pestis.

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Citation: Olson RM, Anderson DM (2019) Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestisin the murine model. PLoS ONE 14(5): e0217440. https://doi.org/10.1371/journal.pone.0217440

Editor: Matthew B. Lawrenz, University of Louisville School of Medicine, UNITED STATES

Received: February 24, 2019; Accepted: May 10, 2019; Published: May 23, 2019

Copyright: © 2019 Olson, Anderson. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript.

Funding: Financial support for this work came from the National Institutes of Health/ National Institute of Allergy and Infectious Disease, public health service award #R01A129996 (DA). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Yersinia pestis; Pneumonic plague; Septicemic plague; Sepsis; Animal models.

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