Christopher Penfold

Lecturer and Course Director for MSc in Molecular Medical Microbiology, Faculty of Medicine & Health Sciences

Contact

workRoom WA1328C A Floor, West Block
Queen's Medical Centre
Nottingham
NG7 2UH
UK
work0115 8467957
fax0115 8468002
chris.penfold@nottingham.ac.uk

Expertise Summary

Normal 0 false false false EN-GB X-NONE X-NONE MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Colicins are protein antibiotics produced by strains of Escherichia coli to kill non-producing strains of the same organims presumably as a method of competitive inhibition. Colicins molecules have three domains that are intrinsically linked to deliver the colicin from the outer membrane to the cytotoxic site of action; either the cytoplasmic membrane or the cytosol. The colicin system continues to generate exciting data about this amazing biological system that addresses several fundamental problems that are poorly understood at the molecular level: (1) Early steps in filamentous bacteriophage infection. Many phages share the same translocation machinery with colicins and possibly the same mechanism for traversing the OM; (2) Host protein function. The functions of host systems that are subverted by colicins such as the Tol-Pal complex remain unresolved even though they are important and ubiquitous in Gram-negative bacteria; (3) Protein recruitment by natively disordered regions (NDRs). NDRs are functionally important in proteins throughout the three kingdoms of life as well as being implicated in cancer, amyloid diseases and bacterial pathogenesis. We have discovered novel recruitment mechanisms used by enzymatic colicin NDRs to bind soluble and membrane-bound proteins in preparation for cellular import; (4) Protein translocation across membranes. How proteins are translocated across membrane barriers is a key issue in the biological and biomedical sciences. A quarter of the E. coli proteome is extracytoplasmic, targeted to a final destination by short, canonical N-terminal sequences that for the most part direct them either to the general secretory or Tat pathway machines. Nuclease colicins are also targeted but in the opposite direction, across both membrane barriers and by a mechanism that is insensitive to the structure of the imported enzyme.

Teaching Summary

Research Summary

Recent Publications

OLUYOMBO, OLUBUKOLA, PENFOLD, CHRISTOPHER N. and DIGGLE, STEPHEN P., 2019. Competition in Biofilms between Cystic Fibrosis Isolates of Pseudomonas aeruginosa Is Shaped by R-Pyocins MBIO. 10(1),
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

View all publications

Normal 0 false false false EN-GB X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} The majority of my teaching encompasses the biology of unicellular micro-organisms and their interaction with multicellular organisms that is essential to our understanding of disease processes, the treatment of bacterial infections and the development of possible chemotherapeutic agents. My teaching is primarily focused on the latest molecular tools that are currently available to research and diagnostic laboratories as cutting edge developments in our fight against the most resilient micro-organisms. I have realized over the last seven years of training that this subject material is best taught through a combination of teaching methods that complement each other in order to increase the impact of the learning environment and improve the quality of teaching. As a result I employ a range of innovative teaching methods such as interactive lectures, laboratory classes, small group tutorials, problem based learning (PBL), e-learning resources such as animated tutorials, and one-to-one consultations. I have instigated a variety of multiple choice questions papers delivered online through a range of on-line software.

I teach on:

MBD301: Introduction to Molecular Microbiology
MBD409: Microbial and Molecular techniques (practical sessions)
MBD403: Applied Molecular Microbiology
MBD402: Research Methods
MBD407: Scientififc review of writing

MSc Clinical Microbiology

MBDDGM: Diagnostic and Laboratory methods Normal 0 false false false EN-GB X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}
MO4MOL: Research Project

BMedsci

Clinical Laboratory Sciences

Current Research

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.

OLUYOMBO, OLUBUKOLA, PENFOLD, CHRISTOPHER N. and DIGGLE, STEPHEN P., 2019. Competition in Biofilms between Cystic Fibrosis Isolates of Pseudomonas aeruginosa Is Shaped by R-Pyocins MBIO. 10(1),
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
JAMES, R., PENFOLD, C. N., MOORE, G. R. and KLEANTHOUS, C., 2002. Killing of E. coli cells by E group nuclease colicins Biochimie. VOL 84(NUMBER 5-6), 381-389
CARR, S., PENFOLD, C. N., BAMFORD, V., JAMES, R. and HEMMINGS, A. M., 2000. The structure of TolB, an essential component of the tol-dependent translocation system, and its protein-protein interaction with the translocation domain of colicin E9 Structure. VOL 8(NUMBER 1), 57-66
PENFOLD, C. N., GARINOT-SCHNEIDER, C., HEMMINGS, A. M., MOORE, G. R., KLEANTHOUS, C. and JAMES, R., 2000. A 76-residue polypeptide of colicin E9 confers receptor specificity and inhibits the growth of vitamin B~1~2-dependent Escherichia coli 113/3 cells Molecular Microbiology. VOL 38(PART 3), 639-649
GARINOT-SCHNEIDER, C., PENFOLD, C. N., MOORE, G. R., KLEANTHOUS, C. and JAMES, R., 1997. Identification of residues in the putative TolA box which are essential for the toxicity of the endonuclease toxin colicin E9 Microbiology. VOL 143(NUMBER 9), 2931-2938
PENFOLD, C. N., BENDER, C. L. and TURNER, J. G., 1996. Characterisation of genes involved in biosynthesis of coronafacic acid, the polyketide component of the phytotoxin coronatine Gene. VOL 183(NUMBER 1/2), 167-173
PENFOLD, C. N., RINGELING, P. L., DAVY, S. L., MOORE, G. R., MCEWAN, A. G. and SPIRO, S., 1996. Isolation, characterisation and expression of the bacterioferritin gene of Rhodobacter capsulatus FEMS Microbiology Letters. VOL 139(NUMBER 2/3), 143-148