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.