MARTIN BADER
Senior Fellow
University of Washington
HSB, Box K155
Seattle, WA 98195
1-5233
mbader
Research Interest:
My past and current research interests have mostly evolved around the question of "how do membrane proteins work?" I am currently studying the membrane-bound histidine kinase PhoQ, which promotes virulence of a variety of gram-negative bacterial pathogens. Histidine sensor-kinases are signaling proteins that play an essential role during many aspects of bacterial physiology including bacterial infections. It is currently unknown how these receptors process and transduce information across the membrane. We found that antimicrobial peptides - short and membrane-active peptides synthesized by the innate immune system - constitute signals that are directly sensed by PhoQ. We found that antimicrobial peptides and divalent cations compete for binding to a highly acidic region of PhoQ suggesting that antimicrobial peptides initiate activation of PhoQ by displacing bound divalent cations. Our findings reveal a molecular mechanism by which bacteria sense small innate immune molecules to initiate a transcriptional program that promotes bacterial virulence.
Publications:
Bader, M. , Sanowar, S. , Delay, M. , Schneider, A., Klevit, R., Le Moual, H. , and Miller, S.I. (2005) Recognition of antimicrobial peptides by a bacterial sensor kinase ( in revision)
Cho, U., Bader, M. , Amaya, M.F., Daley, M., Kelvit, R., Miller, S.I., and Xu, C. (2005) Metal bridges between the PhoQ sensor domain and the membrane regulate transmembrane signaling (in revision)
Miller, S.I., Ernst, R.K., and Bader, M. (2005) Innate Immunity and Infectious Disease Diversity. Nature Reviews Microbiology 3, 36-46
Bader, M., Navarre, W.W., Shiau, W., Nikaido, H., Frye, J.G., McClelland, M., Fang, F.C., and Miller, S.I. (2003) Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides. Molecular Microbiology 50, 219-230
Bader, M. , Hiniker, A., Regeimbal, J., Goldstone, D., Haebel, P., Metcalf, P., and Bardwell, J.C. (2001) Turning a disulfide isomerase into an oxidase. EMBO J. 20, 1555
Bader, M. , Xie, T., Yu C.A., and Bardwell J.C. (2000) Disulfide bonds are generated by quinone reduction. Journal of Biological Chemistry 275, 26082-26088
Bader, M. , Muse, W., Ballou, D.P., Gassner, C., and Bardwell J.C. (1999) Oxidative protein folding is driven by the electron transport system. Cell 98, 217-227
