title: Global metabolomic analysis of a mammalian host infected with Bacillus anthracis.
abstract: Whereas DNA provides the information to design life and proteins provide the materials to construct it, the metabolome can be viewed as the physiology that powers it. As such, metabolomics, the field charged with the study of the dynamic small-molecule fluctuations that occur in response to changing biology, is now being used to study the basis of disease. Here, we describe a comprehensive metabolomic analysis of a systemic bacterial infection using Bacillus anthracis, the etiological agent of anthrax disease, as the model pathogen. An organ and blood analysis identified approximately 400 metabolites, including several key classes of lipids involved in inflammation, as being suppressed by B. anthracis. Metabolite changes were detected as early as 1 day postinfection, well before the onset of disease or the spread of bacteria to organs, which testifies to the sensitivity of this methodology. Functional studies using pharmacologic inhibition of host phospholipases support the idea of a role of these key enzymes and lipid mediators in host survival during anthrax disease. Finally, the results are integrated to provide a comprehensive picture of how B. anthracis alters host physiology. Collectively, the results of this study provide a blueprint for using metabolomics as a platform to identify and study novel host-pathogen interactions that shape the outcome of an infection.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Chinh T Q
authors.initials: CT
authors.lastname: Nguyen
authors.affiliation: Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Vivekananda
authors.initials: V
authors.lastname: Shetty
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA maresso@bcm.edu.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Maresso
mesh_terms: D000818:Animals; D000881:Anthrax / Q000378:metabolism* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001408:Bacillus anthracis / Q000472:pathogenicity* / Q000502:physiology; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D001798:Blood Proteins / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007659:Ketones / Q000494:pharmacology; D055442:Metabolome; D051379:Mice; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013171:Spores, Bacterial / Q000254:growth & development; D016019:Survival Analysis
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001798:Blood Proteins; D007659:Ketones; C400481:PLIalpha; C030325:anthrax toxin; C109341:palmitoyl trifluoromethyl ketone; D054467:Phospholipases A2