Background

Roles and Responsibilities

Qualifications

Ph.D. Microbial Genetics, University of Leeds

B.Sc. Biological Sciences, University of London

Memberships

Honorary Member of the Microbiology Society

Royal Society of Biology (Fellow) 

I am a member of the Biosciences Institute, and my work contributes to the Molecular and Cellular Microbiology research theme.

Research

I am a member of the Biosciences Institute, and my work contributes to the Molecular and Cellular Microbiology research theme.

Research Interests

Microbial protein secretion

Microbial responses to environmental stress

Microbial gene expression and regulatory networks

Genomics and functional analysis of Bacillus species

Antibiotic resistance transfer and regulatory issues concerning antibiotic resistance

Host genome refactoring for the production of specific metabolites and proteins

Current Work

Optimisation of Bacillus subtilis for the secretion of heterologous and industrial proteins and enzymes

Therapeutic proteins (including those required for experimental purposes and clinical trials) are major products of biomanufacturing processes and considerable time and expense are expended to maximise the yield and quality of proteins produced in heterologous hosts. The production host of choice is the Gram-negative bacterium Escherichia coli for which many strains and expression systems have been developed. However, one size does not fit all: E. coli is not suitable for the production of many proteins, either because it is not able to carry out appropriate post-translational modifications (e.g. glycosylation) or because it does not facilitate their folding into a native (i.e. functional) configuration. The former can be overcome by use of more expensive eukaryotic host production systems, while the latter can often be overcome by secreting proteins from the cytoplasm. Secretion has three major potential advantages over intracellular accumulation: the secreted target protein is usually natively folded; yields can be as high or higher than that obtained from intracellular E. coli host/vector systems; there is a reduced requirement for expensive extraction and purification procedures, with reduced risks of contamination with host proteins and nucleic acids.

Although various microbial protein secretion systems have been developed, all currently have limitations that restrict their use and value as a tool for the Biomanufacturing industry. These systems include secretion into the periplasm of E. coli and subsequent selective release and purification; production in the yeast Pichia pastoris; production in Bacillus subtilis and close relatives. In all cases, the yields are relatively low compared with that of the intracellular E. coli systems (mg rather than g per litre).

Bacillus subtilis is widely used for the commercial production of industrial enzymes, particularly for the food and detergents’ industries. Its advantage is its capacity to secrete native Bacillus proteins into the culture medium at concentrations in excess of ten of grams per litre. However, experience with the use of this bacterium for the production of heterologous proteins has been mixed with, in most cases, generally low yields. The aim of this proposal is to exploit knowledge of the genomics and systems biology of B. subtilis to develop this bacterium as a host/vector system for the production of high quality heterologous proteins for clinical trials and for high-throughput X-ray crystallographic studies. The aim is not to replace E. coli as the primary host for heterologous protein production, but to expand the range of host/vector systems that are available for problematical proteins.

Response of Bacillus spp. to environmental and host stresses  

Bacterial evolution is driven by environmental stresses and the need to both survive and compete. For example, infectious disease is the culmination of a battle between the pathogen and its host. Central to the host’s innate defence mechanism are phagocytic cells; macrophages and dendritic cells. Phagocytes express a series of antibacterial factors, including reactive oxygen and nitrogen species, antibacterial peptides and enzymes. They can also impose increased acidification. In spite of these defence mechanisms, several clinically important pathogens can proliferate inside macrophages. The interaction between Bacillus anthracis and host macrophages is central to its pathogenesis. However, an understanding of the cellular and molecular interactions between B. anthracis and the immune system is far from complete. B. anthracis avoids and even breaches cells of the immune system: vegetative cells avoid macrophages by virtue of their possession of a poly-D-glutamic acid capsule, while engulfment of spores by alveolar macrophages and their subsequent efficient germination within the macrophage is an important component of its ability to cause infection. However, it is not clear if B. anthracis can multiply in macrophages. We have dissected the B. anthracis-macrophage relationship through a combination of cellular, genetic and molecular approaches in comparison with a related environmental bacterium, Bacillus subtilis.

Regulatory issues associated innate and acquired antibiotic resistance

I work with European companies and trade organisation to address the issue of antibiotic resistance associated with industrial organisms use for feed and food. A key issue is the identification of innate resistance genes, that tend to remain stably associated with their host organism, and resistance genes associated with mobile genetic elements (MGEs) that are responsible for the widespread spread of antibiotic resistance organisms in the environment. In recent years we have collaborated with colleagues in civil engineering to develop and monitor the transmission of antibiotic resistance genes in water treatment plants. 

Postgraduate Supervision

Yes

Esteem Indicators

Elected Honorary Member of the Microbiology Society

Former Treasurer, Council Member and Publications Officer of the Microbiology Society

Treasurer and Board Member of the Federation of European Microbiology Societies (FEMS)

Former Board Member and Chair of the Finance Strategy Committee of the European Federation of Biotechnology (EFB)

Former Coordinator of two EU FP6 Programme

Advisor to European and Japanese Industrial Biotechnology companies 

Funding

EPSRC

BBSRC

TSB/Innovate UK

European Commission

Industrial Relevance

Biomanufacturing and regulatory issues concerning antibiotic resistance and secondary metabolite synthesis

Patents

1.Harwood, C.R., Stephenson, K., Jørgensen, S.T., Jensen, C.L., and Kristensen, T. (1999) Improved prokaryotic expression of proteins. International Patent. PCT/GB98/01051

2.Harwood, C.R., Stephenson, K., Sarvas. M and Kontinen, V. (1999)

Protein secretion. International Patent PCT/GB99/02191

Teaching

Undergraduate Teaching

BGM1004 - Genetics

CMB3000 - Research Project 

Postgraduate Teaching

PhD students

Publications

• Articles

  • Harwood CR, Kikuchi Y. The ins and outs of Bacillus proteases: activities, functions and commercial significance. FEMS Microbiology Reviews 2022, 46(1), fuab046.
  • Cleverley RM, Webb D, Middlemiss S, Clare AS, Okano K, Harwood CR, Aldred N. In vitro oxidative crosslinking of recombinant barnacle cyprid cement gland proteins. Marine Biotechnology 2021, 23, 928-942.
  • Huang Y, Smith W, Harwood C, Wipat A, Bacardit J. Computational Strategies for the Identification of a Transcriptional Biomarker Panel to Sense Cellular Growth States in Bacillus subtilis. Sensors 2021, 21(7), 2436.
  • Jong M-C, Harwood CR, Blackburn A, Snape JR, Graham DW. Impact of Redox Conditions on Antibiotic Resistance Conjugative Gene Transfer Frequency and Plasmid Fate in Wastewater Ecosystems. Environmental Science and Technology 2020, 54(23), 14984–14993.
  • Almond J, Hacker J, Harwood C, Pizza M, Rappuoli R, Ron EZ, Sansonetti P, Vanderslott S, Wieler LH. Development of vaccines at the time of COVID-19. microLife 2020, 1(1).
  • Al-Zahrani IA, Azhar EI, Jiman-Fatani AA, Siddig LA, Yasir M, Al-Ghamdi AK, Harwood CR. Impact of mass migrations on the clonal variation of clinical Staphylococcus aureus strains isolated from the Western region of Saudi Arabia. Journal of Infection and Public Health 2019, 12(3), 317-322.
  • Sauer C, van Themaat EVL, Boender LGM, Groothuis D, Cruz R, Hamoen LW, Harwood CR, van Rij T. Exploring the Nonconserved Sequence Space of Synthetic Expression Modules in Bacillus subtilis. ACS Synthetic Biology 2018, 7(7), 1773-1784.
  • Jong M-C, Su J-Q, Bunce JT, Harwood CR, Snape JR, Zhu Y-G, Graham DW. Co-optimization of sponge-core bioreactors for removing total nitrogen and antibiotic resistance genes from domestic wastewater. Science of the Total Environment 2018, 634, 1417-1423.
  • Borriss R, Danchin A, Harwood CR, Médigue C, Rocha EPC, Sekowska A, Vallenet D. Bacillus subtilis, the model Gram-positive bacterium: 20 years of annotation refinement. Microbial Biotechnology 2018, 11(1), 3-17.
  • Glenwright H, Pohl S, Navarro F, Miro E, Jiménez G, Blanch AR, Harwood CR. The Identification of Intrinsic Chloramphenicol and Tetracycline Resistance Genes in Members of the Bacillus cereus Group (sensu lato). Frontiers in Microbiology 2017, 7, 1-15.
  • Gilbert C, Howarth M, Harwood CR, Ellis T. Extracellular Self-Assembly of Functional and Tunable Protein Conjugates from Bacillus subtilis. ACS Synthetic Biology 2017, 6, 957-967.
  • Sauer C, Syvertsson S, Bohorquez LC, Cruz R, Harwood CR, van Rij T, Hamoen LW. Effect of Genome Position on Heterologous Gene Expression in Bacillus subtilis: An Unbiased Analysis. ACS Synthetic Biology 2016, 5(9), 942-947.
  • Ulyanova V, Vershinina V, Ilinskaya O, Harwood CR. Binase-like guanyl-preferring ribonucleases are new members of Bacillus PhoP regulon. Microbiological Research 2015, 170, 131-138.
  • Flanagan K, Cockell S, Harwood C, Hallinan J, Nakjang S, Lawry B, Wipat A. A distributed computational search strategy for the identification of diagnostics targets: Application to finding aptamer targets for methicillin-resistant staphylococci. Journal of Integrative Bioinformatics 2014, 11(2), 242.
  • Pohl S, Bhavsar G, Hulme J, Bloor AE, Misirli G, Leckenby MW, Radford DS, Smith W, Wipat A, Williamson ED, Harwood CR, Cranenburgh RM. Proteomic analysis of Bacillus subtilis strains engineered for improved production of heterologous proteins. Proteomics 2013, 13(22), 3298-3308.
  • Krishnappa L, Dreisbach A, Otto A, Goosens VJ, Cranenburgh RM, Harwood CR, Becher D, Maarten van Dijl J. Extracytoplasmic Proteases Determining the Cleavage and Release of Secreted Proteins, Lipoproteins, and Membrane Proteins in Bacillus subtilis. Journal of Proteome Research 2013, 12(9), 4101-4110.
  • Tu WY, Pohl S, Gizynski K, Harwood CR. The Iron-Binding Protein Dps2 Confers Peroxide Stress Resistance on Bacillus anthracis. Journal of Bacteriology 2012, 194(5), 925-931.
  • Flanagan K, Nakjang S, Hallinan J, Harwood C, Hirt RP, Pocock MR, Wipat A. Microbase2.0: a generic framework for computationally intensive bioinformatics workflows in the cloud. Journal of Integrative Bioinformatics 2012, 9(2), 12.
  • Buescher JM, Liebermeister W, Jules M, Uhr M, Muntel J, Botella E, Hessling B, Kleijn RJ, Le Chat L, Lecointe F, Mäder U, Nicolas P, Piersma S, Rügheimer F, Becher D, Bessieres P, Bidnenko E, Denham EL, Dervyn E, Devine KM, Doherty G, Drulhe S, Felicori L, Fogg M, Goelzer A, Hansen A, Harwood CR, Hecker M, Hubner S, Hultschig C, Jarmer H, Klipp E, Leduc A, Lewis P, Molina F, Noirot P, Peres S, Pigeonneau N, Pohl S, Rasmussen S, Rinn B, Schaffer M, Schnidder J, Schwikowski B, Van Dijl JM, Veiga P, Walsh S, Wilkinson AJ, Stelling J, Aymerich S, Sauer U. Global network reorganization during dynamic adaptations of Bacillus subtilis metabolism. Science 2012, 335(6072), 1099-1103.
  • Newman JA, Hewitt L, Rodrigues C, Solovyova AS, Harwood CR, Lewis RJ. Dissection of the network of interactions that links RNA processing with glycolysis in the Bacillus subtilis degradosome. Journal of Molecular Biology 2012, 416(1), 121-136.
  • Nicolas P, Mäder U, Dervyn E, Rochat T, Leduc A, Pigeonneau N, Bidnenko E, Marchadier E, Hoebeke M, Aymerich S, Becher D, Bisicchia P, Botella E, Delumeau O, Doherty G, Denham EL, Fogg M, Fromion V, Goelzer A, Hansen A, Härtig E, Harwood CR, Homuth G, Jarmer H, Jules M, Klipp E, Le Chat L, Lecointe F, Lewis P, Liebemeister W, March A, Mars RAT, Nannapaneni P, Noone D, Pohl S, Rinn B, Rügheimer F, Sappa PK, Samson F, Schaffer M, Schwikowski B, Steil L, Stülke J, Wiegert T, Devine K, Wilkinson AJ, van Dijl JM, Hecker M, Völker U, Bessières P, Noirot P. Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis. Science 2012, 335(6072), 1103-1106.
  • Tu WY, Pohl S, Summpunn P, Hering S, Kerstan S, Harwood CR. Comparative analysis of the responses of related pathogenic and environmental bacteria to oxidative stress. Microbiology 2012, 158, 636-647.
  • Tu WY, Pohl S, Gray J, Robinson NJ, Harwood CR, Waldron KJ. Cellular Iron Distribution in Bacillus anthracis. Journal of Bacteriology 2012, 194(5), 932-940.
  • Newman JA, Hewitt L, Rodrigues C, Solovyova A, Harwood CR, Lewis RJ. Unusual, dual endo- and exonuclease activity in the degradosome explained by crystal structure analysis of RNaseJ1. Structure 2011, 19(9), 1241-1251.
  • Stadler LKJ, Hoffmann T, Tomlinson DC, Song Q, Lee T, Busby M, Nyathi Y, Gendra E, Tiede C, Flanagan K, Cockell SJ, Wipat A, Harwood C, Wagner SD, Knowles MA, Davis JJ, Keegan N, KoFerrigno P. Structure-function studies of an engineered scaffold protein derived from Stefin A. II: Development and applications of the SQT variant. Protein Engineering Design and Selection 2011, 24(9), 751-763.
  • Al-Zahrani IA, Hamson C, Edge D, Collins J, Perry JD, Raza M, Gould K, Harwood CR. SmaI restriction site-based multiplex PCR for typing of hospital and community acquired Staphylococcus aureus. Journal of Clinical Microbiology 2011, 49(11), 3820-3828.
  • van der Ploeg R, Mader U, Homuth G, Schaffer M, Denham EL, Monteferrante CG, Miethke M, Marahiel MA, Harwood CR, Winter T, Hecker M, Antelmann H, van Dijl JM. Environmental Salinity Determines the Specificity and Need for Tat-Dependent Secretion of the YwbN Protein in Bacillus subtilis. PLoS ONE 2011, 6(3), e18140.
  • Dzhongova E, Harwood CR, Thennadil SN. Effect of Sample Thickness on the Extracted Near-Infrared Bulk Optical Properties of Bacillus subtilis in Liquid Culture. Applied Spectroscopy 2011, 65(11), 1314-1320.
  • Pohl S, Tu WY, Aldridge PD, Gillespie C, Hahne H, Mäder U, Read TD, Harwood CR. Combined proteomic and transcriptomic analysis of the response of Bacillus anthracis to oxidative stress. Proteomics 2011, 11(15), 3036-3055.
  • Pohl S, Harwood CR. Heterologous protein secretion by bacillus species from the cradle to the grave. Advances in Applied Microbiology 2010, 73, 1-25.
  • Dzhongova E, Harwood CR, Thennadil SN. Changes in the Absorption and Scattering Properties in the Near-Infrared Region During the Growth of Bacillus subtilis in Liquid Culture. Applied Spectroscopy 2009, 63(1), 25-32.
  • Craddock T, Harwood CR, Hallinan J, Wipat A. e-Science: relieving bottlenecks in large-scale genome analyses. Nature Reviews in Microbiology 2008, 6(12), 948-954.
  • Harvie DR, Andreini C, Cavallaro G, Meng W, Connolly BA, Yoshida K-I, Fujita Y, Harwood CR, Radford DS, Tottey S, Cavet JS, Robinson NJ. Predicting metals sensed by ArsR-SmtB repressors: Allosteric interference by a non-effector metal. Molecular Microbiology 2006, 59(4), 1341-1356.
  • Allenby NEE, Watts CA, Homuth G, Pragai Z, Wipat A, Ward AC, Harwood CR. Phosphate starvation induces the sporulation killing factor of Bacillus subtilis. Journal of Bacteriology 2006, 188(14), 5299-5303.
  • Antelmann H, Williams RC, Miethke M, Wipat A, Albrecht D, Harwood CR, Hecker M. The extracellular and cytoplasmic proteomes of the non-virulent Bacillus anthracis strain UM23C1-2. Proteomics 2005, 5(14), 3684-3695.
  • Allenby NEE, O'Connor N, Pragai Z, Ward AC, Wipat A, Harwood CR. Genome-wide transcriptional analysis of the phosphate starvation stimulon of Bacillus subtilis. Journal of Bacteriology 2005, 187(23), 8063-8080.
  • Pragai Z, Allenby NEE, O'Connor N, Dubrac S, Rapoport G, Msadek T, Harwood CR. Transcriptional Regulation of the phoPR Operon in Bacillus subtilis. Journal of Bacteriology 2004, 186(4), 1182-1190.
  • Shaw OJ, Harwood C, Steggles LJ, Wipat A. SARGE: A tool for creation of putative genetic networks. Bioinformatics 2004, 20(18), 3638-3640.
  • Allenby NEE, O'Connor N, Pragai Z, Carter NM, Miethke M, Engelmann S, Hecker M, Wipat A, Ward AC, Harwood CR. Post-transcriptional regulation of the Bacillus subtilis pst operon encoding a phosphate-specific ABC transporter. Microbiology 2004, 150(8), 2619-2628.
  • Williams RC, Rees ML, Jacobs MF, Pragai Z, Thwaite JE, Baillie LWJ, Emmerson PT, Harwood CR. Production of Bacillus anthracis protective antigen is dependent on the extracellular chaperone, PrsA. Journal of Biological Chemistry 2003, 278(20), 18056-18062.
  • Sandén AM, Prytz I, Tubulekas I, Förberg C, Le H, Hektor A, Neubauer P, Prágai Z, Harwood C, Ward A, Picon A, De Mattos JT, Postma P, Farewell A, Nyström T, Reeh S, Pedersen S, Larsson G. Limiting factors in Escherichia coli fed-batch production of recombinant proteins. Biotechnology and Bioengineering 2003, 81(2), 158-166.
  • Prytz I, Sanden AM, Nystrom T, Farewell A, Wahlstrom A, Forberg C, Pragai Z, Barer M, Harwood C, Larsson G. Fed-batch production of recombinant β-galactosidase using the universal stress promoters uspA and uspB in high cell density cultivations. Biotechnology and Bioengineering 2003, 83(5), 595-603.
  • Kobayashi K, Ehrlich SD, Albertini A, Amati G, Andersen KK, Arnaud M, Asai K, Ashikaga S, Aymerich S, Bessieres P, Boland F, Brignell SC, Bron S, Bunai K, Chapuis J, Christiansen LC, Danchin A, Debarbouille M, Dervyn E, Deuerling E, Devine K, Devine SK, Dreesen O, Errington J, Fillinger S, Foster SJ, Fujita Y, Galizzi A, Gardan R, Eschevins C, Fukushima T, Haga K, Harwood CR, Hecker M, Hosoya D, Hullo MF, Kakeshita H, Karamata D, Kasahara Y, Kawamura F, Koga K, Koski P, Kuwana R, Imamura D, Ishimaru M, Ishikawa S, Ishio I, Le Coq D, Masson A, Mauel C, Meima R, Mellado RP, Moir A, Moriya S, Nagakawa E, Nanamiya H, Nakai S, Nygaard P, Ogura M, Ohanan T, O'Reilly M, O'Rourke M, Pragai Z, Pooley HM, Rapoport G, Rawlins JP, Rivas LA, Rivolta C, Sadaie A, Sadaie Y, Sarvas M, Sato T, Saxild HH, Scanlan E, Schumann W, Seegers JFML, Sekiguchi J, Sekowska A, Seror SJ, Simon M, Stragier P, Studer R, Takamatsu H, Tanaka T, Takeuchi M, Thomaides HB, Vagner V, Van Dijl JM, Watabe K, Wipat A, Yamamoto H, Yamamoto M, Yamamoto Y, Yamane K, Yata K, Yoshida K, Yoshikawa H, Zuber U, Ogasawara N. Essential Bacillus subtilis genes. Proceedings of the National Academy of Sciences 2003, 100(8), 4678-4683.
  • Radford DS, Kihlken MA, Borrelly GPM, Harwood CR, Le Brun NE, Cavet JS. CopZ from Bacillus subtilis interacts in vivo with a copper exporting CPx-type ATPase CopA. FEMS Microbiology Letters 2003, 220(1), 105-112.
  • Radford DS, Kihlken MA, Borrelly GPM, Harwood CR, Le Brun NE, Robinson NJ, Cavet JS. CopZ Cu-metallochaperone from Bacillus subtilis interacts in vivo with Cu-induced Cu-exporter CopA, but enhances Cu atoms per cell. FEMS Microbiology Letters 2003, 220(1), 105-112.
  • Stephenson K, Jensen CL, Jorgensen ST, Harwood CR. Simultaneous inactivation of the wprA and dltB genes of Bacillus subtilis reduces the yield of α-amylase. Letters in Applied Microbiology 2002, 34(6), 394-397.
  • Pragai Z, Harwood CR. Regulatory interactions between the Pho and sigma(B)-dependent general stress regulons of Bacillus subtilis. Microbiology 2002, 148(5), 1593-1602.
  • Thwaite JE, Baillie LWJ, Carter NM, Stephenson K, Rees M, Harwood CR, Emmerson PT. Optimization of the cell wall microenvironment allows increased production of recombinant Bacillus anthracis protective antigen from B-subtilis. Applied and Environmental Microbiology 2002, 68(1), 227-234.
  • Harwood CR, Wipat A, Pragai Z. Functional analysis of the Bacillus subtilis genome. Methods in Microbiology 2002, 33, 337-367.
  • Harwood CR, Moszer I. From gene regulation to gene function: Regulatory networks in Bacillus subtilis. Comparative and Functional Genomics 2002, 3(1), 37-41.
  • Smith RJ, Newton AT, Harwood CR, Barer MR. Active but nonculturable cells of Salmonella enterica serovar Typhimurium do not infect or colonize mice. Microbiology 2002, 148, 2717-2726.
  • Harwood CR, Crawshaw SG, Wipat A. From genome to function: Systematic analysis of the soil bacterium Bacillus subtilis. Comparative and Functional Genomics 2001, 2(1), 22-24.
  • Pragai Z, Eschevins C, Bron S, Harwood CR. Bacillus subtilis NhaC, an Na⁺/H⁺ antiporter, influences expression of the phoPR operon and production of alkaline phosphatases. Journal of Bacteriology 2001, 183(8), 2505-2515.
  • Pragai Z, Harwood CR. YsxC, a putative GTP-binding protein essential for growth of Bacillus subtilis 168. Journal of Bacteriology 2000, 182(23), 6819-6823.
  • Kimmitt PT, Harwood CR, Barer MR. Toxin gene expression by Shiga toxin-producing Escherichia coli: The role of antibiotics and the bacterial SOS response. Emerging Infectious Diseases 2000, 6(5), 458-465.
  • Stephenson K, Jensen CL, Jorgensen ST, Lakey JH, Harwood CR. The influence of secretory-protein charge on late stages of secretion from the Gram-positive bacterium Bacillus subtilis. Biochemical Journal 2000, 350(1), 31-39.
  • Hyyrylainen H-L, Vitikainen M, Thwaite J, Wu H, Sarvas M, Harwood CR, Kontinen VP, Stephenson K. D-alanine substitution of teichoic acids as a modulator of protein folding and stability at the cytoplasmic membrane/cell wall interface of Bacillus subtilis. Journal of Biological Chemistry 2000, 275(35), 26696-26703.
  • Jensen CL, Stephenson K, Jorgensen ST, Harwood C. Cell-associated degradation affects the yield of secreted engineered and heterologous proteins in the Bacillus subtilis expression system. Microbiology 2000, 146(10), 2583-2594.
  • Lahooti M, Harwood CR. Transcriptional analysis of the Bacillus subtilis teichuronic acid operon. Microbiology 1999, 145(12), 3409-3417.
  • Kimmitt PT, Harwood CR, Barer MR. Induction of type 2 Shiga toxin synthesis in Escherichia coli 0157 by 4-quinolones. Lancet 1999, 353(9164), 1588-1589.
  • Bolhuis A, Tjalsma H, Stephenson K, Harwood CR, Venema G, Bron S, Van Dijl JM. Different mechanisms for thermal inactivation of Bacillus subtilis signal peptidase mutants. Journal of Biological Chemistry 1999, 274(22), 15865-15868.
  • Stephenson K, Bron S, Harwood CR. Cellular lysis in Bacillus subtilis; the affect of multiple extracellular protease deficiencies. Letters in Applied Microbiology 1999, 29(2), 141-145.
  • D. B. Kell, A. S. Kaprelyants, D. H. Weichart, C. R. Harwood and M. R. Barer. Viability and activity in readily culturable bacteria: a review and discussion of the practical issues. Antonie Van Leeuwenhoek International Journal of General and Molecular Microbiology 1998, 73, 169-187.
  • Wipat A, Brignell SC, Guy BJ, Rose M, Emmerson PT, Harwood CR. The yvsA-yvqA (293°-289°) region of the Bacillus subtilis chromosome containing genes involved in metal ion uptake and a putative sigma factor. Microbiology 1998, 144(6), 1593-1600.
  • K. Stephenson, N. M. Carter, C. R. Harwood, M. F. Petit-Glatron and R. G. Chambert. The influence of protein folding on late stages of the secretion of alpha-amylases from Bacillus subtilis. Febs Letters 1998, 430, 385-389.
  • J. P. Muller and C. R. Harwood. Protein secretion in phosphate-limited cultures of Bacillus subtilis 168. Applied Microbiology and Biotechnology 1998, 49, 321-327.
  • M. R. Barer, A. S. Kaprelyants, D. H. Weichart, C. R. Harwood and D. B. Kell. Microbial stress and culturability: conceptual and operational domains. Microbiology-UK 1998, 144, 2009-2010.
  • K. Stephenson and C. R. Harwood. Influence of a cell-wall-associated protease on production of alpha-amylase by Bacillus subtilis. Applied and Environmental Microbiology 1998, 64, 2875-2881.
  • V. Parro, R. P. Mellado and C. R. Harwood. Effects of phosphate limitation on agarase production by Streptomyces lividans TK21. Fems Microbiology Letters 1998, 158, 107-113.
  • Kunst F, Ogasawara N, Moszer I, Albertini AM, Alloni G, Azevedo V, Bertero MG, Bessieres P, Bolotin A, Borchert S, Borriss R, Boursier L, Brans A, Braun M, Brignell SC, Bron S, Brouillet S, Bruschi CV, Caldwell B, Capuano V, Carter NM, Choi S-K, Codani J-J, Connerton IF, Cummings NJ, Daniel RA, Denizot F, Devine KM, Dusterhoft A, Ehrlich SD, Emmerson PT, Entian KD, Errington J, Fabret C, Ferrari E, Foulger D, Fritz C, Fujita M, Fujita Y, Fuma S, Galizzi A, Galleron N, Ghim S-Y, Glaser P, Goffeau A, Golightly EJ, Grandi G, Guiseppi G, Guy BJ, Haga K, Haiech J, Harwood CR, Henaut A, Hilbert H, Holsappel S, Hosono S, Hullo M-F, Itaya M, Jones L, Joris B, Karamata D, Kasahara Y, Klaerr-Blanchard M, Klein C, Kobayashi Y, Koetter P, Koningstein G, Krogh S, Kumano M, Kurita K, Lapidus A, Lardinois S, Lauber J, Lazarevic V, Lee S-M, Levine A, Liu H, Masuda S, Mauel C, Medigue C, Medina N, Mellado RP, Mizuno M, Moestl D, Nakai S, Noback M, Noone D, O'Reilly M, Ogawa K, Ogiwara A, Oudega B, Park S-H, Parro V, Pohl TM, Portetelle D, Porwollik S, Prescott AM, Presecan E, Pujic P. The complete genome sequence of the gram-positive bacterium Bacillus subtilis. Nature 1997, 390(6657), 249-256.
  • J. P. Muller, Z. D. An, T. Merad, I. C. Hancock and C. R. Harwood. Influence of Bacillus subtilis phoR on cell wall anionic polymers. Microbiology-Uk 1997, 143, 947-956.
  • Gothel SF, Schmid R, Wipat A, Carter NM, Emmerson PT, Harwood CR, Marahiel MA. An internal FK506-binding domain is the catalytic core of the prolyl isomerase activity associated with the Bacillus subtilis trigger factor. European Journal of Biochemistry 1997, 244(1), 59-65.
  • Fnlmerson P-I, Brignell C, Wipat A, Cartez N, Pragia Z, Guy BJ, Harwood CR. A putative DNA repair operon in B. subtilis comprising a gene encoding a DNA repair polymerase, a routs homolog and an unidentified. FASEB Journal 1997, 11(9), A1368-.
  • Wipat A, Carter N, Brignell SC, Guy BJ, Piper K, Sanders J, Emmerson PT, Harwood CR. The dnaB-pheA (256°-240°) region of the Bacillus subtilis chromosome containing genes responsible for stress responses, the utilization of plant cell walls and primary metabolism. Microbiology 1996, 142(11), 3067-3078.
  • Harwood CR, Wipat A. Sequencing and functional analysis of the genome of Bacillus subtilis strain 168. FEBS Letters 1996, 389(1), 84-87.
  • Gerth U, Wipat A, Harwood CR, Carter N, Emmerson PT, Hecker M. Sequence and transcriptional analysis of clpX, a class-III heat-shock gene of Bacillus subtilis. Gene 1996, 181(1-2), 77-83.
  • C. Eymann, H. Mach, C. R. Harwood and M. Hecker. Phosphate-starvation-inducible proteins in Bacillus subtilis: A two-dimensional gel electrophoresis study. Microbiology-UK 1996, 142, 3163-3170.
  • Lewis PJ, Nwoguh CE, Barer MR, Harwood CR, Errington J. Use of digitized video microscopy with a fluorogenic enzyme substrate to demonstrate cell- and compartment-specific gene expression in Salmonella enteritidis and Bacillus subtilis. Molecular Microbiology 1994, 13, 655-662.
  • SCOTT NW, HARWOOD CR. MECILLINAM SUSCEPTIBILITY OF ESCHERICHIA-COLI K-12-MUTANTS DEFICIENT IN THE ADENOSINE-3',5'-MONOPHOSPHATE SYSTEM. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 1981, 19(4), 540-544.
  • SCOTT NW, HARWOOD CR. STUDIES ON THE INFLUENCE OF THE CYCLIC-AMP SYSTEM ON MAJOR OUTER-MEMBRANE PROTEINS OF ESCHERICHIA-COLI-K12. FEMS MICROBIOLOGY LETTERS 1980, 9(2), 95-98.

• Book Chapters

  • Harwood CR, Pohl S, Smith W, Wipat A. Bacillus subtilis: Model Gram-Positive Synthetic Biology Chassis. In: Colin Harwood and Anil Wipat, ed. Microbial Synthetic Biology. Oxford: Academic Press, 2013, pp.87-117.
  • Brown A, Snape JR, Harwood CR, Head IM. Whole genome microarray analysis of the expression profile of Escherichia coli in response to exposure to para-nitrophenol. In: Hogstrand, C; Kille, P, ed. Comparative Toxicogenomics. Amsterdam; Boston: Elsevier, 2008, pp.221-248.

• Conference Proceedings (inc. Abstracts)

  • Craddock T, Lord P, Harwood C, Wipat A. e-science tools for the genomic scale characterisation of bacterial secreted proteins. In: Proceedings of the UK e-Science All Hands Meeting 2006. 2006, Nottingham, UK: National e-Science Centre.
  • SCOTT NW, HARWOOD CR. MORPHOLOGY OF MUTANTS OF ESCHERICHIA-COLI-K12 DEFICIENT IN THE CYCLIC-AMP SYSTEM. In: HEREDITY. 1979.

• Edited Book

  • Harwood CR, Wipat A, ed. Systems Biology of Bacteria. Oxford: Academic Press, 2012.

• Editorial

  • Harwood CR, Park SH, Sauer M. Editorial for the thematic issue on "Industrial Microbiology". FEMS Microbiology Letters 2018, 365(24), fny275.

• Letter

  • Hamson C, Walton KE, Collins J, Wilson L, Perry JD, Al-Zahrani IA, Harwood CR. Report of an outbreak of CO2-dependent methicillin-resistant Staphylococcus aureus on a regional liver transplant unit. Journal of Antimicrobial Chemotherapy 2011, 66(5), 1179-1181.

• Note

  • Cleverley R, Webb D, Middlemiss S, Duke P, Clare A, Okano K, Harwood C, Aldred N. Correction to: In Vitro Oxidative Crosslinking of Recombinant Barnacle Cyprid Cement Gland Proteins (Marine Biotechnology, (2021), 23, 6, (928-942), 10.1007/s10126-021-10076-x). Marine Biotechnology 2022, 24, 430.

• Reviews

  • Harwood CR, Bouillon JM, Pohl S, Arnau J. Secondary metabolite production and the safety of industrially important members of the Bacillus subtilis group. FEMS Microbiology Reviews 2018, 42(6), 721-738.
  • Brown A, Snape JR, Harwood CR, Head IM. Whole genome microarray analysis of the expression profile of Escherichia coli in response to exposure to para-nitrophenol. Advances in Experimental Biology 2008, 2, 221-248.
  • Harwood CR, Cranenburgh R. Bacillus protein secretion: an unfolding story. Trends in Microbiology 2008, 16(2), 73-79.
  • Sarvas M, Harwood CR, Bron S, Van Dijl JM. Post-translocational folding of secretory proteins in Gram-positive bacteria. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2004, 1694(1-3), 311-327.
  • Wipat A, Harwood CR. The Bacillus subtilis genome sequence: The molecular blueprint of a soil bacterium. FEMS Microbiology Ecology 1999, 28(1), 1-9.
  • Barer MR, Harwood CR. Bacterial viability and culturability. Advances in Microbial Physiology 1999, 41(0), 93-137.