People Detail

Faculty Biography For:

Anne Delcour
Ph.D, Cornell University, 1986

Biology and Biochemistry Department
University of Houston
Houston, Texas 77204-5001

Office: SR2 221D
Phone: (713) 743-2684

I am interested in the molecular mechanisms of ion channel function and modulation. In particular, my lab is focused on the study of bacterial ion channels because bacteria are a convenient system where electrophysiological, biochemical and genetic studies can be performed. We use the patch clamp and planar lipid bilayer techniques to measure the electrical activity of single channel proteins in real time. The computer analysis of the data gives us information on the size and selectivity of the ion channel, kinetic properties, dependence on transmembrane voltage or on other physical or chemical parameters, and mechanisms of modulation. These techniques are widely used in the investigation of eukaryotic channels, in particular those of neurons.

We are in the process of characterizing the molecular properties of various Escherichia coli and Vibrio cholerae channels. Most of our effort is devoted to the study of porins, abundant channels of the outer membrane. These proteins play an essential role in the flux of nutrients, ions, signaling molecules and antibiotics inside the cell, and their study is of great interest not only in the broad scope of fundamental research on ion channels and bacterial physiology, but also with respect to potential medical applications and antibiotic resistance. Our goal is to understand the molecular mechanisms underlying the spontaneous oscillations of the channels between open and closed states, and modulation of these ion channels by voltage, pH and other relevant metabolites. They are one of the few ion channels whose structure is known at atomic resolution. This gives us the excellent opportunity to investigate the relationships between structure and function by performing electrophysiological and biochemical experiments on both spontaneously occurring and genetically engineered mutant channels.

Current projects include the characterization of the major diffusion porins of Vibrio cholerae OmpU and OmpT, and their mutants. Studies by Dr. Karl Klose have shown that the artificial expression of OmpT in V. cholerae cells inside the host, instead of the normal expression of OmpU, leads to attenuation of virulence and defects in colonization. OmpU and OmpT are fairly similar at the sequence level, but have profound functional differences. Our aim is to understand the molecular basis of these differences through structure-function relationship analysis and studies on modulation. In particular we are focusing our efforts on the modulation of channel activity by acidic pH and by bile acids. Altogether, this work will lead to a better understanding of the role of porins in virulence and adaptation to the host environment. Similar projects are also undertaken on the porins of E. coli; in particular we are studying the effect of loop mutations in the general diffusion porin OmpF on the channel response to acidic pH.

Recently, we have also developed new projects to characterize the outer membrane components of bacterial secretion machineries. These components are believed to form regulated pores to allow the transit of secreted proteins to the cell surface. Bacteria export a vast array of proteins, such as toxins, enzymes, adhesins, and cell surface appendages, many of which play important roles in the virulence of pathogenic species. The molecular mechanisms by which the outer membrane pores recognize and transport their cognate substrates are poorly understood. We are currently investigating the electrophysiological properties of some of these protein-transporting channels in a variety of micro-organisms. In particular, we have two ongoing collaborations with Dr. David Thanassi (Stony Brook) on the PapC usher of uropathogenic E. coli, and with Dr. Hye-Jeong Yeo (UH) on the TpsB of the two-partner secretion system of H. influenzae.

Duret, G. and Delcour, A.H., Size and dynamics of the Vibrio cholerae porins OmpU and OmpT probed by polymer exclusion, Biophys. J. 98:1820-1829 (2010).

Pagel, M. and Delcour, A. H. Effects of conjugated and unconjugated bile acids on the activity of the Vibrio cholerae porin OmpT, Molec. Membr. Biology 28:69-78 (2011).

Mapingire, O.S., Henderson, N.S., Duret, G., Thanassi, D.G. and Delcour, A.H., Modulating Effects of the Plug, Helix and N- and C-terminal Domains on Channel Properties of the PapC Usher, J. Biol. Chem. 284:36324-36333 (2009)

Wager, B, Baslé, A and Delcour, A. H. Disulfide bond tethering of extracellular loops does not affect the closure of OmpF porin at acidic pH, Proteins 78:2886-2894 (2010).

Delcour, A. H., Outer Membrane Permeability and Antibiotic Resistance, Bioph. Biochim. Acta - Proteins and Proteomics 1794:808-816 (2009)

Duret, G., Szmanski, M.., Choi, K.-J., Yeo, H.-J., and Delcour, A. H., The TpsB Translocator HMW1B of Hemophilus influenzae Forms a Large-Conductance Channel, J. Biol. Chem. 283:15771-15778 (2008)

Duret, G., Simonet, V. and Delcour, A. H., Modulation of Vibrio cholerae Porin Function by Acidic pH, Channels 1:70-79 (2007)

Pagel, M., Simonet, V., Li, J., Lallemand, M., Lauman, B., and Delcour, A. H., Phenotypic Characterization of Pore Mutants of the Vibrio cholerae Porin OmpU, J. Bacteriol. 189:8593-8600 (2007).

Duret, G. and Delcour, A. H., Deoxycholic Acid Blocks Vibrio cholerae OmpT but not OmpU Porin, J. Biol. Chem., 281:19899-19905 (2006)

Baslé, A., Qutub, R., Mehrazin, M., Wibbenmeyer, J. A. and Delcour, A. H., Deletions of Single Extracellular Loops Affect pH-Sensitivity, but not Voltage-Dependence, of the E. coli Porin OmpF, Prot. Engineering Design and Selection, 17:665-672 (2004).

Baslé, A., Iyer, R. and Delcour, A. H., Subconductance States in OmpF Porin Gating, Biochim. Biophys. Acta, 1664:100-107 (2004)

Simonet, V. C., Baslé, A., Klose, K. E. and Delcour, A. H., The Vibrio cholerae Porins OmpU and OmpT Have Distinct Channel Properties, J. Biol. Chem. 278: 17539-17545 (2003).

Delcour, A. H., Solute Uptake through General Porins. Front. Biosci. 8, d1055-1071 (2003).

Samartzidou, H, Mehrazin, M., Xu, Z., Benedik, M. J. and Delcour, A. H., Cadaverine Inhibition of Porin Plays a Role in Cell Survival at Acidic pH, J. Bacteriol. 185: 13-19 (2003).

Bredin J, Simonet V, Iyer R, Delcour AH, Pagès JM. (2003). Colicins, spermine and cephalosporins: a competitive interaction with the OmpF eyelet. Biochemical Journal, 376(Pt 1):245-52.

Wibbenmeyer, J.A., Provenzano, D., Landry, C., Klose, K. and Delcour, A. H., Vibrio porins OmpT and OmpU Are Differentially Affected by Bile, Infect. Immun. 70:121-126 (2002).

Delcour, A. H.,  Structure and Function of Pore-Forming beta-Barrels from Bacteria, J. Mol. Micro. Biotechnol. 4:1-10  (2002)

Wibbenmeyer JA, Provenzano D, Landry CF, Klose KE, Delcour AH. (2002). Vibrio cholerae OmpU and OmpT porins are differentially affected by bile. Infection And Immunity, 70(1):121-6.

Liu, N., Samartzidou, H., Lee, K.-W., Briggs, J. and Delcour, A. H., Effects of Pore Mutations and Permeant Ion Concentration on the Spontaneous Gating Activity of OmpC Porin, Protein Engineering 13:491-500 (2000).

Iyer, R., Wu, Z., Woster, P. M. and Delcour, A. H., Molecular Basis for the Polyamine - OmpF Porin Interactions: Inhibitor and Mutant Studies, J. Mol. Biol. 297:933-945 (2000).

Samartzidou, H. and Delcour, A. H., Excretion of Endogenous Cadaverine Leads to a Decrease in Porin-Mediated Outer Membrane Permeability, J. Bacteriol. 181: 791-798 (1999).

Samartzidou, H. and Delcour, A. H., E. coli PhoE Porin Has an Opposite Voltage Dependence from the Homologous OmpF. EMBO J. , 17:93-100 (1998).

Delcour, A. H., Function and Modulation of Porins: Insights from Electrophysiology FEMS Microbiol. Lett. 151:115-123 (1997).

Iyer, R. and Delcour, A. H., Complex Inhibition of OmpF and OmpC Bacterial Porins by Polyamines. J. Biol. Chem. 272:18595-18601 (1997).

delaVega, A.L. and Delcour, A. H., Cadaverine Induces Closing of E. coli Porins.EMBO Journal 14:6058-6065 (1995).