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School of Life Sciences
 

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Kim Hardie

Professor and Co-director of National Biofilms Innovation Centre, Faculty of Medicine & Health Sciences

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Biography

The rise in antimicrobial resistance is at at the point of crisis, and novel antimicrobial strategies are required. We are searching for novel antimicrobial targets to combat this. The co-ordinated communities that bacteria form on surfaces (biofilms) are especially resistant to antimicrobials, so we are interrogating these at a single cell level in real time to investigate the metabolic status of the bacteria and the characteristics of their closest environmental microniches. We are doing this in collaboration with leading scientists internationally, and using state-of-the-art technologies including Raman spectroscopy, OrbiSIMS and optical nanosensors. We are also investigating specific virulence strategies. Autotransporter proteins are the largest family of bacterial secreted proteins, and all of those characterized to date are virulence factors. One area we study is the characterization of the secretion pathway they use to exit the cell in the molecular detail. The second project focuses on cell-cell signaling molecules involved in population density related gene regulation. The bacteria we are studying include Pseudomonas aeruginosa, Escherichia coli and Staphylococcus. We have two translational projects, one focuses on studying single bacterial cells in real time during skin infections using our range of infection models that include polymicrobial communities, and the other aims to design and build novel interactive devices to help children wash their hands effectively, and thereby avoid spreading dangerous infectious agents. Associated public engagement activities have been recognized by the award of the 2023 Outreach Prize by the Microbiology Society.

Governance roles as a trustee of the Microbiology Society () and the Royal Society of Biology () alongside being deputy co-director of the National Biofilms Innovation Centre () have received recognition by the nomination and admittance into the Freedom of the City of London by Redemption by the Lord Mayor Professor Mainielli in October 2024.

Expertise Summary

I have extensive experience in molecular microbiology, including imaging, biofilm infection models, protein biochemistry and genetic engineering. I have also been involved in numerous studies of gene regulation and more recently am becoming familiar with analytical chemistry techniques aimed at elucidating the metabolome of bacteria. Furthermore, I am expanding my knowledge of tissue engineering and vibrational spectroscopy alongside developing mechanisms to commercialise my research.

Teaching Summary

To convey knowledge about bacterial pathogenicity and to provide pastoral support and mentor students

Research Summary

Protein secretion enables the bacterium to place a battery of offense (toxins, proteases, etc) and defense (flagella, S-layers) systems beyond the boundaries of their outermembrane. The question `how do such large, sometimes folded structures exit the bacterial cell without causing cell leakage?' is fascinating, but little is known about the mechanics involved. I am interested in characterising these machineries in respect to autotransporter proteins, and determining their role in infection. Gene regulation (particularly that of virulence factors) plays a major role in cell survival and pathogenesis by controlling cell fitness and virulence. My group investigates the integration of metabolism with cell-cell communication, in particular in biofilms to understand the fitness and antimicrobial resistance of bacteria and how this impacts upon pathogenesis. The aim is to uncover and develop novel antiicrobial strategies.

Selected Publications

  • KASZA, K, RICHARDS, B, JONES, S, ROMERO, M, ROBERTSON, S, HARDIE, K.R, GURNANI, P, C脕MARA, M and ALEXANDER, C, 2024. ACS Applied Materials & Interfaces.
  • HARDIE, K.R, SELF, T and MARKUS, R, 2024. Journal of Physics: conference series.
  • DUBERN J-F, HALLIDAY N, C脕MARA M, WINZER K, BARRETT DA, HARDIE KR, WILLIAMS P, 2023. Growth rate and nutrient limitation as key drivers of extracellular quorum sensing signal molecule accumulation in Pseudomonas aeruginosa. Microbiology. 169, 001316
  • SOH, E. Y-C.,, SMITH, F, GIMENEZ, M.R.,, YAN, L., VERJBORG, R.M.,, FLETCHER, M, HALLIDAY, N.,, BLEVES, S, HEEB, S, CAMARA, M, GIVSKOV, M, HARDIE, K.R, TOLKER-NIELSEN, T, B脡RENG脠RE, I. and WILLIAMS, P, 2021. PLoS Pathogens.

Past Research

My Career has focused on the mechanism of bacterial protein secretion, its regulation and relevance to pathogenicity with the overall aim to discover novel antimicrobials. In Cambridge I worked with Profs Colin Hughes and Vassilis Koronakis on the type I dependent secretion of haemolysin (HlyA) from E. coli. Then, in Canada with Prof Tom Buckley on the type II dependent secretion of aerolysin by Aeromonas hydrophila. Moving to Institut Pasteur, Paris with Tony Pugsley, I switched to study the secretion apparatus, concentrating on the outer membrane component GspD and associated GspS. Subsequently I have studied AHL-dependent quorum sensing with Paul Williams (Nottingham) and the survival of H. pylori exposed to different stress conditions, particularly iron availability and oxidative stress, with the aim of discovering the function of the NapA protein (with Robert Logan and Peter Jenks). In collaboration with John Atherton I was involved in characterizing the link between the two major virulence factors of H. pylori (Vacuolating cytotoxin and Cag pathogenicity Island). Motility is an important virulence factor for H. pylori, and in collaboration with Dr Liz Sockett (Department of Genetics) and Klaus Winzer I studied the role of FlhB in flagella assembly and function. The secretion of botulinum toxins via the flagella of Clostridia was investigated with Nigel Minton, and in collaboration with Christoph Tang (Imperial College), Prof Paul Williams (Nottingham), Prof John Atherton (Nottingham), Prof Jerry Wells (Holland) and Klaus Winzer (Nottingham), we studied the role of quorum sensing (cell-cell communication) in H. pylori, C. jejuni, P. aeruginosa, and N. meningitidis, linking this to pathogenicity. With the help of Dave Barrett (Nottingham) we also linked quorum sensing signal molecule production to its impact on cellular metabolism and the consequences this has to cell fitness and virulence (with Nigel Halliday, Cath Otori, Jean Dubern, Avika Ruparell). A major part of my research has focused on the mechanism of autotransporter protein secretion in E. coli (with Jeni Luckett [Nottingham], Rob Delahay [Nottingham], Ian Henderson [Australia] and Luis Angel Fernandez Herrero [Madrid]), Pseudomonas aeruginosa (with Miguel Camara [Nottingham], Stephan Heeb [Nottingham], and Alain Filloux [Imperial College]), Bordetella pertussis (Francoise Jacob Dubuisson [Lille]) and H. pylori (Paul O'Toole, Ireland). Together we aimed at dissecting the roles of potential accessory proteins in this process. With Joel Segal (Engineering Nottingham), Jacqueline Randle and Natalie Vaughan (Nursing ), and Brigitte Nerlich (Nottingham) , I have developed interactive ways of improving the hand hygiene of children and integrated this with a range of outreach activities including the Royal Society Summer Exhibition 2019 with Morgan Alexander [Nottingham]..

Future Research

I shall continue to study aspects of quorum sensing, metabolism and bacterial protein secretion. In addition I am looking forward to a new project centred around determining simultaneous measurement of transcription, translation and metabolism during human skin infection and in polymicrobial biofilms.

  • HARDIE, K.R, SELF, T and MARKUS, R, 2024. Journal of Physics: conference series.
  • KASZA, K, RICHARDS, B, JONES, S, ROMERO, M, ROBERTSON, S, HARDIE, K.R, GURNANI, P, C脕MARA, M and ALEXANDER, C, 2024. ACS Applied Materials & Interfaces.
  • KASZA, K, SOUKARIEH, F, ROMERO, M, HARDIE, K.R, GURNANI, P, C脕MARA, M and ALEXANDER, C, 2024. RSC Applied Polymers.
  • DUBERN J-F, HALLIDAY N, C脕MARA M, WINZER K, BARRETT DA, HARDIE KR, WILLIAMS P, 2023. Growth rate and nutrient limitation as key drivers of extracellular quorum sensing signal molecule accumulation in Pseudomonas aeruginosa. Microbiology. 169, 001316
  • KASZA, K, ELSHERBENY, A, MOLONEY, C, HARDIE, K.R, CAMARA, M, ALEXANDER, C and GURNANI, P, 2023. Macromolecular Chemistry and Physics.
  • HARDIE, K.R and FENN, S.J, 2022. Journal of Medical Microbiology.
  • SOH, E. Y-C.,, SMITH, F, GIMENEZ, M.R.,, YAN, L., VERJBORG, R.M.,, FLETCHER, M, HALLIDAY, N.,, BLEVES, S, HEEB, S, CAMARA, M, GIVSKOV, M, HARDIE, K.R, TOLKER-NIELSEN, T, B脡RENG脠RE, I. and WILLIAMS, P, 2021. PLoS Pathogens.
  • HOLLMANN, B.,, PERKINS, M, CHAUHAN, V.M, AYLOTT, J.W., and HARDIE, K.R, 2021. NPJ Biofilms and Microbiomes.
  • ZHANG, JUNTING, BROWN, JAMES, SCURR, DAVID J., BULLEN, ANWEN, MACLELLAN-GIBSON, KIRSTY, WILLIAMS, PAUL, ALEXANDER, MORGAN R., HARDIE, KIM R., GILMORE, IAN S. and RAKOWSKA, PAULINA D., 2020. ANALYTICAL CHEMISTRY. 92(13), 9008-9015
  • JORDANA-LLUCH, ELENA, GARCIA, VANINA, KINGDON, ALEXANDER D. H., SINGH, NISHANT, ALEXANDER, CAMERON, WILLIAMS, PAUL and HARDIE, KIM R., 2020. FRONTIERS IN MICROBIOLOGY. 11,
  • BARZAN, G., A, SACCO, A.,, MANDRILE, L.,, GIOVANNOZZI, A.M, BROWN, J, PORTESI, C, EXANDER, M, WILLIAMS, P, HARDIE, K.R. and ROSSI, A.M, 2020. Sensors and Actuators B: Chemical.
  • SINGH N, ROMERO M, TRAVANUT A, MONTEIRO PF, JORDANA-LLUCH E, HARDIE KR, WILLIAMS P, ALEXANDER MR and ALEXANDER C, 2019. Biomaterials science. 7(10), 4099-4111
  • LARY, D., CALVERT, A., NERLICH, B., SEGAL, J., VAUGHAN, N., RANDLE, J. and HARDIE, K. R., 2019. Journal of Infection Prevention.
  • HARDIE K, 2019. Available at: <https://microbiologysociety.org/publication/current-issue/metabolism-health-and-disease/article/where-bacterial-metabolism-and-virulence-intersect.html>
  • BROWN, J.M, WILLIAMS, P and HARDIE, K.R, 2019.
  • RUPARELL A, DUBERN JF, ORTORI CA, HARRISON F, HALLIDAY NM, EMTAGE A, ASHAWESH MM, LAUGHTON CA, DIGGLE SP, WILLIAMS P, BARRETT DA and HARDIE KR, 2016. Scientific reports. 6, 33101
  • JACQUELINE RANDLE, JAMES METCALFE, HELENA WEBB, JENI CA LUCKETT, BRIGITTE NERLICH, NATHALIE VAUGHAN, JOEL SEGAL and KIM R HARDIE, 2014. BioMed Frontiers in infection.
  • BABAN ST, KUEHNE SA, BARKETI-KLAI A, CARTMAN ST, KELLY ML, HARDIE KR, KANSAU I, COLLIGNON A and MINTON NP, 2013. PloS one. 8(9), e73026
  • RANDLE J, METCALFE J, WEBB H, LUCKETT JCA, NERLICH B, VAUGHAN N, SEGAL JI and HARDIE KR, 2013. The Journal of hospital infection. 85(3), 220-5
  • ESTEBAN PAREDES-OSSES and KIM R HARDIE, 2013. Bio-protocol.
  • LUCKETT, J.C.A., DARCH, O., WATTERS, C., ABUOUN, M., WRIGHT, V., PAREDES-OSSES, E., WARD, J., GOTO, H., HEEB, S., POMMIER, S., RUMBAUGH, K.P., C脕MARA, M. and HARDIE, K.R., 2012. PLoS Pathogens. 8(8), e1002854
  • ORTORI, C.A, DUBERN J-F, C脕MARA M.G, HARDIE K.R, WILLIAMS P and BARRETT D.A., 2011. Analytical Bioanalytical Chemistry. 399(2), 839-850
  • HALLIDAY, N M, HARDIE, K R, WILLIAMS, P, WINZER, K and BARRETT, D A, 2010. Analytical Biochemistry. 403(1-2), 20-9
  • DOHERTY, N. C., SHEN, F., HALLIDAY, N. M., BARRETT, D. A., HARDIE, K. R., WINZER, K. and ATHERTON, J. C., 2010. Journal of Bacteriology. 192, 1184 - 1192
  • SHEN, F., HOBLEY, L., DOHERTY, N., LOH, J.T., COVER, T.L., SOCKETT, R.E., HARDIE, K.R. and ATHERTON, J.C., 2010. BMC Microbiology. 10, 210
  • O'TOOLE, P.W., SNELLING, W.J., CANCHAYA, C., FORDE, B.M., HARDIE, K.R., JOSENHANS, C., GRAHAM, R.L.J., MCMULLAN, G., PARKHILL, J., BELDA, E. and BENTLEY, S.D., 2010. BMC Genomics. 11, 164
  • HEURLIER, K., VENDEVILLE, A., HALLIDAY, N., GREEN, A., WINZER, K., TANG, C.M. and HARDIE, K.R., 2009. Journal of Bacteriology. 191(4), 1293-1302
  • HOLMES, K., TAVENDER, T.J., WINZER, K., WELLS, J.M. and HARDIE, K.R., 2009. BMC Microbiology. 9, 214
  • HARDIE, K.R, POMMIER, S and WILHELM, S., 2009. . In: KARL WOOLDRIDGE, ed., Bacterial Secreted Proteins Caister Academic Press. 451-479
  • TAVENDER, TIMOTHY J, HALLIDAY, NIGEL M, HARDIE, KIM R and WINZER, KLAUS, 2008. BMC Microbiology. 8, 98
  • HARDIE, KIM RACHAEL and HEURLIER, KARIN, 2008. Nature Reviews: Microbiology. 6(8), 635-43
  • ARGENT, R.H., THOMAS, R.J., LETLEY, D.P., RITTIG, M.G., HARDIE, K.R. and ATHERTON, J.C., 2008. Journal of Medical Microbiology. 57(2), 145-150
  • WAND, M.E., SOCKETT, R.E., EVANS, K.J., DOHERTY, N., SHARP, P.M., HARDIE, K.R. and WINZER, K., 2006. Journal of Bacteriology. 188(21), 7531-7541
  • FITCHEN, N., LETLEY, D.P., O SHEA, P., ATHERTON, J.C., WILLIAMS, P. and HARDIE, K.R., 2005. Journal of Medical Microbiology. 54(7), 621-630
  • VENDEVILLE, A., WINZER, K., HEURLIER, K., TANG, C. M. and HARDIE, K. R., 2005. Nature Reviews: Microbiology. VOL 3(NUMB 5), 383-396
  • HARDIE, K.R., BALDWIN, T.J. and WILLIAMS, P., 2005. Molecular basis of bacterial adaptation to a pathogenic lifestyle. In: MAHY, B.J., ed., Topley & Wilson's microbiology & microbial infections 10th ed. Volume 1: Bacteriology. London: Hodder Arnold. 146-183
  • FITCHEN, N., WILLIAMS, P. and HARDIE, K.R., 2003. FEMS Microbiology Letters. 229(1), 57-63
  • COOKSLEY, C., JENKS, P. J., GREEN, A., COCKAYNE, A., LOGAN, R. P. H. and HARDIE, K. R., 2003. Journal of Medical Microbiology. VOL 52(PART 6), 461-469
  • THOMAS, R.J., ARGENT, R.H., LETLEY, D.P., HARDIE, K.R. and ATHERTON, J.C., 2003. Interaction between the Helicobacter pylori virulence factors cagA and vacA Gut. 52, 195
  • HARDIE, K.R., COOKSLEY, C., GREEN, A.D. and WINZER, K., 2003. Microbiology. 149(3), 715-728
  • NARAYANAN, G.L., LETLEY, D.P., AVILES, F., BEBB, J.R., HARDIE, K.R. and ATHERTON, J.C., 2003. Gastroenterology. 124(4), A271-A271
  • THOMAS, R.J., ARGENT, R.H., LETLEY, D.P., HARDIE, K.R. and ATHERTON, J.C., 2003. Gastroenterology. 124(4), A272-A272
  • WINZER,K., HARDIE,K.R. and WILLIAMS,P., 2003. LuxS and autoinducer-2: their contribution to quorum sensing and metabolism in bacteria. In: LASKIN, A.I., BENNETT, J.W. and GADD, G.M., eds., Advances in applied microbiology Vol. 53. Elsevier Academic Press. 291-396
  • FITCHEN, N., O'SHEA, P., WILLIAMS, P. and HARDIE, K.R., 2003. Molecular Immunology. 40, 407-411 (In Press.)
  • WINZER, K., HARDIE, K.R., BURGESS, N., DOHERTY, N., KIRKE, D., HOLDEN, M.T.G., LINFORTH, R., CORNELL, K.A., TAYLOR, A.J., HILL, P.J. and WILLIAMS P., 2002. Microbiology. 148(4), 909-922
  • WINZER, K., HARDIE, K.R. and WILLIAMS, P., 2002. Current Opinion in Microbiology. 5(2), 216-222
  • BURGESS, N.A., KIRKE, D.F., WILLIAMS, P., WINZER, K., HARDIE, K.R., MEYERS, N.L., ADUSE-OPOKU, J., CURTIS, M.A. and CAMARA, M., 2002. LuxS-dependent quorum sensing in Porphyromonas gingivalis modulates protease and haemagglutinin activities but is not essential for virulence Microbiology. 148(3), 763-772
  • KAUR, M., JUMEL, K., HARDIE, K. R., HARDMAN, A., MEADOWS, J. and MELIA, C. D., 2002. Journal of Chromatography A. VOL 957(NUMBER 2), 139-148
  • WINZER, K., SUN, Y.-H., GREEN, A., DELORY, M., BLACKLEY, D., HARDIE, K.R., BALDWIN, T.J. and TANG, C.M., 2002. Infection and Immunity. 70(4), 2245-2248
  • GUILVOUT, I., HARDIE, K. R., SAUVONNET, N. and PUGSLEY, A. P., 1999. Genetic Dissection of the Outer Membrane Secretin PulD: Are There Distinct Domains for Multimerization and Secretion Specificity? Journal of Bacteriology. VOL 181(NUMBER 23), 7212-7220
  • JIANG, Y., CAMARA, M., CHHABRA, S. R., HARDIE, K. R., BYCROFT, B. W., LAZDUNSKI, A., SALMOND, G. P. C., STEWART, G. S. A. B. and WILLIAMS, P., 1998. Molecular Microbiology. VOL 28(NUMBER 1), 193-203
  • MCGOWAN, S.J., SEBAIHIA, M., O'LEARY, S., HARDIE, K.R., WILLIAMS, P., STEWART, G.S.A.B., BYCROFT, B.W. and SALMOND, G.P.C., 1997. Molecular Microbiology. 26(3), 545-556
  • DAEFLER, S., GUILVOUT, I., HARDIE, K. R., PUGSLEY, A. P. and RUSSEL, M., 1997. Molecular Microbiology. VOL 24(NUMBER 3), 465-475
  • PUGSLEY, A. P., FRANCETIC, O., POSSOT, O. M., SAUVONNET, N. and HARDIE, K. R., 1997. Gene. VOL 192(NUMBER 1), 13-19
  • PUGSLEY, A. P., FRANCETIC, O., HARDIE, K., POSSOT, O. M., SAUVONNET, N. and SEYDEL, A., 1997. Pullulanase: Model Protein Substrate for the General Secretory Pathway of Gram-Negative Bacteria FOLIA MICROBIOLOGICA -PRAGUE-. VOL 42(NUMBER 3), 184-192
  • HARDIE, K. R., SEYDEL, A., GUILVOUT, I. and PUGSLEY, A. P., 1996. Molecular Microbiology. VOL 22(NUMBER 5), 967-976
  • STANLEY, P., KORONAKIS, V., HARDIE, K. and HUGHES, C., 1996. Molecular Microbiology. VOL 20(NUMBER 4), 813-822
  • HARDIE, K. R., LORY, S. and PUGSLEY, A. P., 1996. Insertion of an outer membrane protein in Escherichia coli requires a chaperone-like protein EMBO Journal. VOL 15(NUMBER 5), 978-988

School of Life Sciences

糖心原创
Medical School
Queen's Medical Centre
Nottingham NG7 2UH

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