Signatures of Antimicrobial Resistance Detectable by Minimally Invasive Means
Abstract
The goals of this work are to identify specific volatile metabolite profiles that are signatures for antimicrobial resistant (AMR)/multidrug resistance (MDR) in Yersinia pestis and Francisella tularensis, characterize these profiles and related protein expression pathways, and demonstrate that these signatures can be sample in a minimally invasive manner. Yersinia pestis is a bacterium that causes the disease plague and F. tularensis is different bacterium that causes the disease tularemia. AMR/MDR is exceedingly rare in Y. pestis and F. tularensis. However, our team includes partners from highly endemic regions that will provide AMR/MDR strains for this study as well as genetically similar susceptible strains to serve as controls. We will create cultures from the AMR/MDR and susceptible Y. pestis and F. tularensis strains and volatile compounds will be collected from these cultures using a dynamic headspace collection approach and captured and stored in sorbent traps. Volatile compounds in these samples will be chemically analyzed by thermal desorption gas chromatography/mass spectrometry. Using existing analysis tools developed to aid in the discovery of volatile markers, the resulting data will be analyzed to identify differences between the AMR/MDR and susceptible strains, and a bottom-up proteomics approach will comprehensively identify the expressed proteins. Significantly different proteins will be used in pathway analysis with the KEGG database, which contains multiple Y. pestis and F. tularensis strains. Pathways differentially regulated between AMR/MDR and the susceptible strains will be used for metabolic pathway analysis. Minimally invasive sampling of identified volatile compounds will be demonstrated with mouse pulmonary infection models. The signatures identified in this basic research study will increase fundamental knowledge and understanding of AMR/MDR in biothreat-relevant microbes and facilitate future improved diagnostic tools to identify drug resistant Y. pestis and F. tularensis.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 13, 2016
- Source ID
- HDTRA11610052
Entities
People
- David M Wagner
Organizations
- Defense Threat Reduction Agency
- Northern Arizona University