A non‐human primate model for Yersinia pestis infection: metabolomic analysis pilot study

Abstract

Yersinia pestis, the etiological agent of the plague, is a potential biothreat agent. Upon inhalation, the Gram‐negative bacterium causes pneumonic plague, a rapidly progressing, severe lung infection that is usually fatal. Only limited work using metabolite profiles to study the progression of the disease has been done, and exact mechanisms that facilitate disease are not well‐characterized. In this study, African Green monkeys were exposed to aerosolized highly virulent Y. pestis CO92 and metabolomic profiling of plasma samples was conducted. Comparison of control counterparts to the disease states at earlier time points (6 hours to 18 hours) versus at later time points (24 hours onwards) showed mainly two‐fold higher increases in the levels of certain polyunsaturated fatty acids, long chain fatty acids and metabolites from fatty acid metabolism pathway. Significant alterations in metabolites related to early inflammation and oxidative stress, increased energy demands to the host, and potential renal dysfunction were revealed. The metabolomics of plasma have the potential to provide a more thorough understanding of the Y. pestis pathogenesis, which may assist future treatment of this disease.The grant # TMTI0029_09_WR_T from Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency is acknowledged.DISCLAIMER“Research was conducted in compliance with the Animal Welfare Act and all other Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.”