Threat Agnostic Virulence Assessment of Pathogens
EMSL Project ID
60276
Abstract
Direct communication with DTRA PM’s have expressed a desire for a more robust approach to threat agnostic virulence prediction. This proposal to develop an assay to detect threats has impact in first responder space and potential wearable sensors. This is of interest to DHS, and our proposed system is highly desirable for monitoring agents in a threat agnostic manner, ultimately enabling a diagnostic assay to be deployed in the field. Virulence assessment of new, emerging, and engineered pathogens is critical to mounting an appropriate response to a biothreat agent. The capacity of the pathogen to colonize human tissues, harm tissues, and evade the host immune cells must be characterized to understand pathogenicity pathways and optimize diagnosis and treatment of resulting disease. Respiratory pathogens are of interest because they can have high transmissibility rates, as observed with the SARS-CoV-2 virus, the causative agent of Covid-19. Current technologies are insufficient to assess threats due to their reliance on systems with only one cell type and on sequencing the pathogen. However, it is known that sequence is not an accurate predictor of function, and sequencing can be unreliable for newly emerged or engineered pathogens. An ideal system would consist of relevant epithelial cell types with an immune system component and an assay sensitive enough to detect changes in host responses that do not rely on DNA sequencing. PNNL has developed a novel co-culture system consisting of host immune cells and lung epithelial cells that can be used to assess the virulence of unknown respiratory pathogens (Hess et al.). We propose to interrogate pathogens using this model and assess features of pathogenicity. Our objective is to leverage PNNLs strengths in tissue engineering and proteomics capabilities to build a multiple reaction monitoring (MRM) or parallel reaction monitoring (PRM) liquid chromatography-tandem mass spectrometry assay for human host cell proteins whose abundance is influenced by infection. These responses can then be assessed for relative virulence using pathogen agnostic signatures.
Project Details
Start Date
2022-02-01
End Date
2022-09-30
Status
Closed
Released Data Link
Team
Principal Investigator