Penfold, Christopher - University of Nottingham

研究领域

Bacteriocins are protein antibiotics produced by strains of bacteria that are active against related bacteria. We are particularly interested in a group of bacteriocins called colicins that are produced by Escherichia coli and are active against other enterobacteriaceae. They are ~60 KDa proteins that consist of three functional domains that allow the colicin to bind to cell surface receptors, move through the cell envelope and then kill the bacterial cell by, for example, degrading the DNA. We are interested in how the DNase domain of colicin E9 is delivered into the cytoplasm of sensitive cells to exert its antibacterial effect. Antimicrobial peptides Antimicrobial peptides are low molecular weight polypeptides that have narrow spectrum activities. Lysostaphin, for example, is produced by Stapholococcus simulans against Staph. aureus and the clinically important MRSA. Lysostaphin has two domains; a targeting domain which binds to an unknown cell surface receptor of S. aureus and a cytotoxic domain which cleaves a pentaglycine cross bridge in the host cell wall. We are interested in conducting a structure/function study of both the targeting and endopeptidase domains of lysostaphin to determine whether it is possible to produce hybrid molecules with more broad spectrum activities.

近期论文

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KIM YC, TARR AW and PENFOLD CN, 2014. Colicin import into E. coli cells: A model system for insights into import mechanisms of bacteriocins. Biochimica et biophysica acta. (In Press.) BANO S, VANKEMMELBEKE M, PENFOLD CN and JAMES R, 2014. Detection of induced synthesis of colicin E9 using ColE9p::gfpmut2 based reporter system. World journal of microbiology & biotechnology. 30(7), 2091-9 LI, C., ZHANG, Y., VANKEMMELBEKE, M., HECHT, O., ALEANIZY, F.S., MACDONALD, C., MOORE, G.R., JAMES, R. and PENFOLD, C.N., 2012. Structural evidence that colicin A protein binds to a novel binding site of TolA protein in Escherichia coli periplasm Journal of Biological Chemistry. 287(23), 19048-19057 PENFOLD, C.N., LI, C., ZHANG, Y., VANKEMMELBEKE, M. and JAMES, R., 2012. Colicin A binds to a novel binding site of TolA in the Escherichia coli periplasm Biochemical Society Transactions. 40(6), 1469-1474 VANKEMMELBEKE M, JAMES R and PENFOLD CN, 2012. Membrane activities of colicin nuclease domains: analogies with antimicrobial peptides. Biochemical Society transactions. 40(6), 1517-21 PENFOLD CN, WALKER D and KLEANTHOUS C, 2012. How bugs kill bugs: progress and challenges in bacteriocin research. Biochemical Society transactions. 40(6), 1433-7 VANKEMMELBEKE, M., O'SHEA. P., JAMES, R. and PENFOLD, C.N., 2012. Interaction of nuclease colicins with membranes: insertion depth correlates with bilayer perturbation PLoS One. 7(9), e46656 HECHT, O., ZHANG, Y., LI, C., PENFOLD, C.N., JAMES, R. and MOORE, G.R., 2010. Characterisation of the interaction of colicin A with its co-receptor TolA FEBS Letters. 584(11), 2249-2252 ZHANG, Y., LI, C., VANKEMMELBEKE, M.N., BARDELANG, P., PAOLI, M., PENFOLD, C.N. and JAMES, R., 2010. The crystal structure of the TolB box of colicin A in complex with TolB reveals important differences in the recruitment of the common TolB translocation portal used by group A colicins Molecular Microbiology. 75(3), 623-636 BARDELANG, P., VANKEMMELBEKE, M., ZHANG, Y., JARVIS, H., ANTONIADOU, E., ROCHETTE, S., THOMAS, N.R., PENFOLD, C.N. and JAMES, R., 2009. Design of a polypeptide FRET substrate that facilitates study of the antimicrobial protease lysostaphin Biochemical Journal. 418, 615-624 VANKEMMELBEKE, M., ZHANG, Y., MOORE, G.R., KLEANTHOUS, C., PENFOLD, C.N. and JAMES, R., 2009. Energy-dependent immunity protein release during tol-dependent nuclease colicin translocation Journal of Biological Chemistry. 284(28), 18932-18941 ZHANG, Y., VANKEMMELBEKE, M.N., HOLLAND, L.E., WALKER, D.C., JAMES, R. and PENFOLD, C.N., 2008. Investigating early events in receptor binding and translocation of colicin E9 using synchronized cell killing and proteolytic cleavage Journal of Bacteriology. 190(12), 4342-4350 WARFIELD, RACHEL, BARDELANG, PHILIP, SAUNDERS, HELEN, CHAN, WENG C, PENFOLD, CHRISTOPHER, JAMES, RICHARD and THOMAS, NEIL R, 2006. Internally quenched peptides for the study of lysostaphin: an antimicrobial protease that kills Staphylococcus aureus. Organic and Biomolecular Chemistry. 4(19), 3626-38 HANDS, S.L., HOLLAND, L.E., VANKEMMELBEKE, M., FRASER, L., MACDONALD, C.J., MOORE, G.R., JAMES, R. and PENFOLD, C.N., 2005. Interactions of TolB with the translocation domain of colicin E9 require an extended TolB box Journal of Bacteriology. 187(19), 6733-6741 TOZAWA, K., MACDONALD, C.J., PENFOLD, C.N., JAMES, R., KLEANTHOUS, C., CLAYDEN, N.J. and MOORE, G.R., 2005. Clusters in an intrinsically disordered protein create a protein-binding site: the TolB-binding region of colicin E9 Biochemistry. 44(34), 11496-11507 VANKEMMELBEKE, M., HEALY, B., MOORE, G.R., KLEANTHOUS, C., PENFOLD, C.N. and JAMES, R., 2005. Rapid detection of colicin E9-induced DNA damage using Escherichia coli cells carrying SOS promoter-lux fusions Journal of Bacteriology. 187(14), 4900-4907 PENFOLD, C.N., HEALY, B., HOUSDEN, N.G., BOETZEL, R., VANKEMMELBEKE, M., MOORE, G.R., KLEANTHOUS, C. and JAMES, R., 2004. Flexibility in the receptor-binding domain of the enzymatic colicin E9 is required for toxicity against Escherichia coli cells Journal of Bacteriology. 186(14), 4520-4527 MACDONALD, C. J., TOZAWA, K., COLLINS, E. S., PENFOLD, C. N., JAMES, R., KLEANTHOUS, C., CLAYDEN, N. J. and MOORE, G. R., 2004. Characterisation of a mobile protein-binding epitope in the translocation domain of colicin E9 Journal of Biomolecular NMR. VOL 30(NUMBER 1), 81-96 LAW, C.J., PENFOLD, C.N., WALKER, D.C., MOORE, G.R., JAMES, R. and KLEANTHOUS, C., 2003. OmpF enhances the ability of BtuB to protect susceptible Escherichia coli cells from colicin E9 cytotoxicity FEBS Letters. 545(2-3), 127-132 COLLINS, E.S., WHITTAKER, S. B.-M., TOZAWA, K., MACDONALD, C., BOETZEL, R., PENFOLD, C.N., REILLY, A., CLAYDEN, N.J., OSBORNE, M.J., HEMMINGS, A.M., KLEANTHOUS, C., JAMES, R. and MOORE, G.R., 2002. Structural dynamics of the membrane translocation domain of colicin E9 and its interaction with TolB Journal of Molecular Biology. 318(3), 787-804