Growing levels of antibiotic resistance make infection caused by Gram negative bacteria a looming public health crisis. The Henderson laboratory uses interdisciplinary approaches to better understand Gram negative virulence and to identify new therapeutic strategies. To do this, we combine patient-oriented studies with new biochemical approaches to identify how virulence-associated bacterial pathogens cause disease. New mathematic approaches to genetic and metabolomic data suggest that distinct evolutionary virulence “strategies” used by a single pathogenic species may manifest as the same disease. Using these results as a guide, we seek a mechanistic understanding of how these virulence-associated properties interact with the host. Of particular interest are multifunctional small molecules associated with iron scavenging – called siderophores. New properties and host interactions have been identified for bacterial siderophores using a combination of biochemical and pathophysiologic approaches including mass spectrometry-based metabolomics, bacterial genetics, protein chemistry, and infection models. Together, these studies are suggesting new therapeutic and diagnostic strategies directed toward Gram negative bacterial infections.


Washington University School of Medicine

Saint Louis, MO

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