Beyond the List: Bioagent-Agnostic Signatures Could Enable a More Flexible and Resilient Biodefense Posture Than an Approach Based on Priority Agent Lists Alone.

Owen P Leiser,Amy C Sims,George W Korch,Karen L Taylor,Errett C Hobbs

doi:10.3390/pathogens10111497

Owen P Leiser, Amy C Sims + Show 3 more

Open Access

https://doi.org/10.3390/pathogens10111497

Copy DOI

Journal: Pathogens	Publication Date: Nov 17, 2021
Citations: 11	License type: CC BY 4.0

Affiliation: Pacific Northwest National Laboratory, Battelle

Abstract

As of 2021, the biothreat policy and research communities organize their efforts around lists of priority agents, which elides consideration of novel pathogens and biotoxins. For example, the Select Agents and Toxins list is composed of agents that historic biological warfare programs had weaponized or that have previously caused great harm during natural outbreaks. Similarly, lists of priority agents promulgated by the World Health Organization and the National Institute of Allergy and Infectious Diseases are composed of previously known pathogens and biotoxins. To fill this gap, we argue that the research/scientific and biodefense/biosecurity communities should categorize agents based on how they impact their hosts to augment current list-based paradigms. Specifically, we propose integrating the results of multi-omics studies to identify bioagent-agnostic signatures (BASs) of disease—namely, patterns of biomarkers that accurately and reproducibly predict the impacts of infection or intoxication without prior knowledge of the causative agent. Here, we highlight three pathways that investigators might exploit as sources of signals to construct BASs and their applicability to this framework. The research community will need to forge robust interdisciplinary teams to surmount substantial experimental, technical, and data analytic challenges that stand in the way of our long-term vision. However, if successful, our functionality-based BAS model could present a means to more effectively surveil for and treat known and novel agents alike.

Highlights

In the United States, biodefense and biosecurity policy as well as biological threat research largely center around several lists of priority agents including the Federal SelectAgent Program (FSAP) Select Agents and Toxins list [1] which is intended to catalog and define security measures for those agents that pose an especially high risk to human, animal, and plant health, the National Institute of Allergy and Infectious Diseases (NIAID)Emerging Infectious Diseases/Pathogens list [2], and the World Health Organization priority pathogens list [3]
We argue that the biodefense and emerging infectious diseases communities should adopt a new strategy to augment—but not replace—list-based approaches
Others in the biodefense community have recognized how too heavily relying on lists limits our biothreat detection, diagnostic, and countermeasure capabilities; the 2018 National Academies of Sciences report on Biodefense in the Age of Synthetic Biology [4] states “an overreliance on the Select Agent List is a systematic weakness affecting many aspects of the United States’

Summary

Introduction

In the United States, biodefense and biosecurity policy as well as biological threat research largely center around several lists of priority agents including the Federal Select. Employing a BAS-based approach to biodefense would shift the community’s focus from characterizing specific pathogenic taxa to a framework that hinges on identifying functional interactions in host networks which drive or enable pathogenesis; recentering our biodefense posture in this way could make it easier to control future biological threats. These signatures would (1) be demonstrative of the specific interactions a pathogen employs to usurp host processes and (2) represent evolutionarily conserved host-response patterns to a wide range of pathogens and toxins that elicit disease. We will focus on humans as the host of interest, but this concept could be valid in categorizing animal and plant host responses

Common Themes in Host Response Could Form the Basis for Establishing BASs

Host Innate Immune Response during Infection

Dysregulation of Iron Homeostasis during Infection

Autophagy

Exploiting the Interactome

Conclusions