Jeffrey P. Henderson, M.D., Ph.D.
Center for Women's Infectious Diseases (cWIDR)
Molecular Microbiology and Microbial Pathogenesis Program
Computational and Molecular Biophysics Program
10306 BJC Institute of Health
bacterial pathogenesis, host-pathogen interactions, iron, mass spectrometry, medicinal chemistry, metabolomics
Biochemistry of the interface between hosts and bacterial pathogens
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.
Shields-Cutler, R.R., Crowley, J.R., Hung, C., Stapleton, A.E., Aldrich, C.C., Marschall, J., Henderson, J.P. “Human Urinary Composition Controls Siderocalin’s Antibacterial Activity”. Journal of Biological Chemistry, April 10, 2015.
Koh E.I., Hung C., Parker K.S., Crowley J.R., Giblin, D.E., Henderson, J.P. “Metal selectivity by the virulence-associated yersiniabactin metallophore system”. Metallomics. March 31, 2015.
Lv, H., Hung, C., Henderson, J.P. “Metabolomic Analysis of Siderophore Cheater Mutants Reveals Metabolic Costs of Expression in Uropathogenic Escherichia coli” J. Proteome Research, 13(3):1397-404. 2014.
Chaturvedi, K.S., Hung, C., Giblin, D.E., Austin, A.M., Dinauer, M.C., Gross, M.L., Henderson, J.P. “Cupric yersiniabactin is a Virulence-Associated Superoxide Dismutase Mimic”, ACS Chemical Biology, 9(2):551-61. 2013.
Chaturvedi, K.S., Hung, C., Crowley, J.R., Stapleton, A.E., Henderson, J.P. “The siderophore yersiniabactin protects uropathogenic Escherichia coli from copper toxicity in vivo”. Nature Chemical Biology, 8, 731–736. 2012.
Lukacik, P., Barnard, T.J., Keller, P.W., Chaturvedi, K.S., Seddiki, N., Fairman, J.W., Noinaj, N., Kirby, T.L., Henderson, J.P., Steven, A.C., Hinnebusch, J., Buchanan, S.K. “Structural engineering of a phage lysin that targets Gram-negative pathogens”. Proceedings of the National Academy of Sciences, U.S.A. 109(25):9857-62 2012.
Marschall, J., Zhang, L., Foxman, B., Warren, D.K., Henderson, J.P., “Both Host and Pathogen Factors Predispose to Escherichia coli Urinary-Source Bacteremia in Hospitalized Patients”. Clinical Infectious Diseases, 54(12):1692-1698. 2012.
Lv H, Henderson JP. Regulatory genes associated with yersiniabactin, a virulence-associated secondary metabolite, alter the Escherichia coli primary metabolome. Journal of Proteome Research. 10 (12), pp 5547–5554, 2011.
Lv H, Hung C, Chaturvedi KS, Hooton TM, Henderson JP. Development of an Integrated Metabolomic Profiling Approach for Infectious Diseases Research. Analyst 2011 136 (22): 4752–4763.
Henderson JP et al. Quantitative metabolomics reveals an epigenetic blueprint for iron acquisition in uropathogenic Escherichia coli. PLoS Pathogens 2009 5(2):e1000305.
Last Updated: 6/12/2015 9:43:08 AM