Faculty of Health and Life Sciences

Dr Stephen Michell

Dr Stephen Michell

Associate Professor of Molecular Microbiology

 S.L.Michell@exeter.ac.uk

 5524

 Geoffrey Pope 405

 

Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK

Overview

I am a molecular microbiologist with interests in the the virulence mechanisms of pathogenic bacteria. My research has focused on the post-translational modification of bacterial proteins and into the development of genetic tools for the manipulation of hazardous pathogens. My lab looks predominantly at secreted proteins, focusing on lipoproteins. We study both Gram negative and positive bacteria, with the aim of characterising novel virulence factors. I am a member of the Microbes and Disease research group.

Qualifications

1993: BSc, Chemistry and Biochemistry, Imperial College.
1999: PhD, St. Mary's Hospital, Imperial College.
2011: Fellow of the Higher Education Academy

Career

2023-Present:  Associate Professor of Molecular Microbiology, Biosciences, University of Exeter

2012-2023: Senior Lecturer of Molecular Microbiology, School of Biosciences, University of Exeter
2007-2012: Lecturer of Molecular Microbiology, School of Biosciences, University of Exeter
2002-2007: Research Scientist at the Defence Science Technology Laboratories
1994-2002: Research Scientist at the Veterinary Laboratories Agency

Links

Research group links

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Research

Research interests

My research aims to identify and characterise novel virulence factors from human pathogens to further understand mechanisms of bacterial pathogenesis. One area of particular interest is bacterial post-translational modification. Several pathogens secrete proteins which are acylated or glycosylated, or both, and function as virulence factors. Understanding the mechanisms by which pathogens modify their proteins and the contribution of these modifications to disease is the main focus of my research. I also have an interest in whole genome sequencing of bacterial pathogens as an approach to identifying novel virulence factors.

Current projects include study of the mechanism of protein acylation by Clostridium difficle and its role in virulence. Identification of novel virulence factors of Vibrio vulnificus. I also have collaborative research projects with Professor Rick Titball looking at Burkholderia pseudomallei and Coxiella Burnetti.

Collaborators

  • Prof Neil Fairweather – Imperial College
  • Prof Nigel Minton – University of Nottingham
  • De Ed Tate – Imperial College
  • Dr Craig Baker-Austin – CEFAS
  • Dr Rosanna Leuzzi – Novartis, Siena
  • Dr Paolo Landini – University of Milan
  • Dr Mona Bajaj-Elliot – University College London
  • Dr Ray Sheridan -Royal Devon & Exeter Hospital
  • Dr Ed Keedwell – CEMPS, University of Exeter

Research grants

  • 2016 NERC
    Development of a diagnostic tool for the identification of Vibrio vulnificus strains associated with disease.
  • 2016 Saved and Safe
    Saved and Safe. Project to develop molecular diagnostics for bovine tuberculosis
  • 2011 Cefas and University of Exeter
    Insights into pathogenesis and virulence using targeted gene disruption of the pathogens Vibrio parahaemolyticus and vulnificus
  • 2010 PenCLARHC
    Exploring the potential for the development of a DNA based diagnostic for Clostridium difficile to indicate probability of relapse
  • 2010 CARIPLO
    From Genome to Antigen
  • 2009 Defence Science and Technology Laboratory
    Galleria Models for Assessing Virulence of B. pseudomallei
  • 2007 Defence Science and Technology Laboratory
    Identification of Genes Involved in Resistance to Bacterial Infection

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Publications

Journal articles

Fletcher J, Manley R, Fitch C, Bugert C, Moore K, Farbos A, Michelsen M, Alathari S, Senior N, Mills A, et al (2024). The Citizen Phage Library: Rapid Isolation of Phages for the Treatment of Antibiotic Resistant Infections in the UK. Microorganisms, 12(2), 253-253. Abstract.
Cotton S, McHugh MP, Dewar R, Haas JG, Templeton K, Consortium TCGU, Robson SC, Connor TR, Loman NJ, Golubchik T, et al (2023). Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes. Journal of Hospital Infection, 135, 28-36.
Kennedy NA, Janjua M, Chanchlani N, Lin S, Bewshea C, Nice R, McDonald TJ, Auckland C, Harries LW, Davies M, et al (2023). Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic. Gut, 72(2), 295-305. Abstract.  Author URL.
Baker S, Dougan G, Hess C, Kingston N, Lehner PJ, Lyons PA, Matheson NJ, Owehand WH, Saunders C, Summers C, et al (2022). Author Correction: SARS-CoV-2 evolution during treatment of chronic infection. Nature, 608(7922), e23-e23.
Baker S, Dougan G, Hess C, Kingston N, Lehner PJ, Lyons PA, Matheson NJ, Owehand WH, Saunders C, Summers C, et al (2022). Author Correction: Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature, 608(7922), e24-e24.
Kläser K, Molteni E, Graham M, Canas LS, Österdahl MF, Antonelli M, Chen L, Deng J, Murray B, Kerfoot E, et al (2022). COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: a prospective observational cohort study. Scientific Reports, 12(1). Abstract.
Aggarwal D, Page AJ, Schaefer U, Savva GM, Myers R, Volz E, Ellaby N, Platt S, Groves N, Gallagher E, et al (2022). Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission. Nature Communications, 13(1).
Aggarwal D, Warne B, Jahun AS, Hamilton WL, Fieldman T, du Plessis L, Hill V, Blane B, Watkins E, Wright E, et al (2022). Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission. Nature Communications, 13(1). Abstract.
Nickbakhsh S, Hughes J, Christofidis N, Griffiths E, Shaaban S, Enright J, Smollett K, Nomikou K, Palmalux N, Tong L, et al (2022). Genomic epidemiology of SARS-CoV-2 in a university outbreak setting and implications for public health planning. Scientific Reports, 12(1). Abstract.
Twohig KA, Nyberg T, Zaidi A, Thelwall S, Sinnathamby MA, Aliabadi S, Seaman SR, Harris RJ, Hope R, Lopez-Bernal J, et al (2022). Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study. The Lancet Infectious Diseases, 22(1), 35-42. Abstract.
Fletcher J, Porter R, Boulton Z, Brown L, Knight B, Romanczuk L, Aiken S, Delury C, Michell S (2022). In vitro efficacy of antibiotic loaded calcium sulfate beads (Stimulan Rapid Cure) against polymicrobial communities and individual bacterial strains derived from diabetic foot infections. J Med Microbiol, 71(5). Abstract.  Author URL.
Robson SC, Connor TR, Loman NJ, Golubchik T, Martinez Nunez RT, Bonsall D, Rambaut A, Snell LB, Ludden C, Corden S, et al (2022). Publisher Correction: Genomic reconstruction of the SARS CoV-2 epidemic in England. Nature, 606(7915), e18-e18.
Willett BJ, Grove J, MacLean OA, Wilkie C, De Lorenzo G, Furnon W, Cantoni D, Scott S, Logan N, Ashraf S, et al (2022). SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway. Nature Microbiology, 7(8), 1161-1179. Abstract.
Ashford F, Best A, Dunn SJ, Ahmed Z, Siddiqui H, Melville J, Wilkinson S, Mirza J, Cumley N, Stockton J, et al (2022). SARS-CoV-2 Testing in the Community: Testing Positive Samples with the TaqMan SARS-CoV-2 Mutation Panel to Find Variants in Real Time. Journal of Clinical Microbiology, 60(4), e02408-e02421.
Volz E, Mishra S, Chand M, Barrett JC, Johnson R, Geidelberg L, Hinsley WR, Laydon DJ, Dabrera G, Toole AO, et al (2021). Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. NATURE, 593(7858), 266-+.  Author URL.
Graham MS, Sudre CH, May A, Antonelli M, Murray B, Varsavsky T, Kläser K, Canas LS, Molteni E, Modat M, et al (2021). Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study. The Lancet Public Health, 6(5), e335-e345.
Volz E, Hill V, McCrone JT, Price A, Jorgensen D, O’Toole Á, Southgate J, Johnson R, Jackson B, Nascimento FF, et al (2021). Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell, 184(1), 64-75.e11.
Elliott P, Haw D, Wang H, Eales O, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, et al (2021). Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant. Science, 374(6574). Abstract.  Author URL.
Vöhringer HS, Sanderson T, Sinnott M, De Maio N, Nguyen T, Goater R, Schwach F, Harrison I, Hellewell J, Ariani CV, et al (2021). Genomic reconstruction of the SARS-CoV-2 epidemic in England. Nature, 600(7889), 506-511. Abstract.
Kemp SA, Collier DA, Datir RP, Ferreira IATM, Gayed S, Jahun A, Hosmillo M, Rees-Spear C, Mlcochova P, Lumb IU, et al (2021). SARS-CoV-2 evolution during treatment of chronic infection. Nature, 592(7853), 277-282. Abstract.
Collier DA, De Marco A, Ferreira IATM, Meng B, Datir RP, Walls AC, Kemp SA, Bassi J, Pinto D, Silacci-Fregni C, et al (2021). Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. NATURE, 593(7857), 136-+.  Author URL.
de Silva TI, Liu G, Lindsey BB, Dong D, Moore SC, Hsu NS, Shah D, Wellington D, Mentzer AJ, Angyal A, et al (2021). The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. iScience, 24(11). Abstract.
Masoli JAH, Jeffries A, Temperton B, Auckland C, Michelsen M, Warwick-Dugdale J, Manley R, Farbos A, Ellard S, Knight B, et al (2021). Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak. Abstract.
Hubert CL, Michell SL (2020). A universal oyster infection model demonstrates that Vibrio vulnificus Type 6 secretion systems have antibacterial activity in vivo. Environ Microbiol, 22(10), 4381-4393. Abstract.  Author URL.
Aanensen DM, Abudahab K, Adams A, Afifi S, Alam MT, Alderton A, Alikhan N-F, Allan J, Almsaud M, Alrezaihi A, et al (2020). An integrated national scale SARS-CoV-2 genomic surveillance network. LANCET MICROBE, 1(3), E99-E100.  Author URL.
Bradshaw WJ, Bruxelle J-F, Kovacs-Simon A, Harmer NJ, Janoir C, Péchiné S, Acharya KR, Michell SL (2019). Molecular features of lipoprotein CD0873: a potential vaccine against the human pathogen Clostridioides difficile. J Biol Chem, 294(43), 15850-15861. Abstract.  Author URL.
Fletcher J, Porter R, Aiken S, Delury C, Michell S (2019). The effect of local release antibiotic beads on in-vitro bacterial growth from tissue taken from infected diabetic foot ulcers. Access Microbiology, 1(1A). Abstract.
Church SR, Lux T, Baker-Austin C, Buddington SP, Michell SL (2016). Vibrio vulnificus Type 6 Secretion System 1 Contains Anti-Bacterial Properties. PLoS One, 11(10). Abstract.  Author URL.
Nandi T, Holden MTG, Didelot X, Mehershahi K, Boddey JA, Beacham I, Peak I, Harting J, Baybayan P, Guo Y, et al (2015). Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles. Genome Res, 25(4).  Author URL.
Nandi T, Holden MTG, Didelot X, Mehershahi K, Boddey JA, Beacham I, Peak I, Harting J, Baybayan P, Guo Y, et al (2015). Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles. Genome Res, 25(1), 129-141. Abstract.  Author URL.
Nandi T, Holden MTG, Didelot X, Mehershahi K, Boddey JA, Beacham I, Peak I, Harting J, Baybayan P, Guo Y, et al (2015). Errata: Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles (Genome Research (2015) 25 (129-141)). Genome Research, 25(4).
Aiken SS, Cooper JJ, Florance H, Robinson MT, Michell S (2015). Local Release of Antibiotics for Surgical Site Infection Management Using High-Purity Calcium Sulfate: an in Vitro Elution Study. SURGICAL INFECTIONS, 16(1), 54-61.  Author URL.
Charlton TM, Kovacs-Simon A, Michell SL, Fairweather NF, Tate EW (2015). Quantitative Lipoproteomics in <i>Clostridium difficile</i> Reveals a Role for Lipoproteins in Sporulation. CHEMISTRY & BIOLOGY, 22(11), 1562-1573.  Author URL.
Peano C, Chiaramonte F, Motta S, Pietrelli A, Jaillon S, Rossi E, Consolandi C, Champion OL, Michell SL, Freddi L, et al (2014). Gene and protein expression in response to different growth temperatures and oxygen availability in Burkholderia thailandensis. PLoS One, 9(3). Abstract.  Author URL.
Kovacs-Simon A, Leuzzi R, Kasendra M, Minton N, Titball RW, Michell SL (2014). Lipoprotein CD0873 is a novel adhesin of Clostridium difficile. J Infect Dis, 210(2), 274-284. Abstract.  Author URL.
Butt E, Foster JAH, Keedwell E, Bell JEA, Titball RW, Bhangu A, Michell SL, Sheridan R (2013). Derivation and validation of a simple, accurate and robust prediction rule for risk of mortality in patients with Clostridium difficile infection. BMC Infect Dis, 13 Abstract.  Author URL.
He M, Miyajima F, Roberts P, Ellison L, Pickard DJ, Martin MJ, Connor TR, Harris SR, Fairley D, Bamford KB, et al (2013). Emergence and global spread of epidemic healthcare-associated Clostridium difficile. Nature Genetics, 45(1), 109-113. Abstract.
Gourlay LJ, Peri C, Ferrer-Navarro M, Conchillo-Solé O, Gori A, Rinchai D, Thomas RJ, Champion OL, Michell SL, Kewcharoenwong C, et al (2013). Exploiting the Burkholderia pseudomallei acute phase antigen BPSL2765 for structure-based epitope discovery/design in structural vaccinology. Chem Biol, 20(9), 1147-1156. Abstract.  Author URL.
Michell SL (2012). A better understanding of what makes some proteins "fat". J Bacteriol, 194(9), 2129-2130.  Author URL.
He M, Miyajima F, Roberts P, Ellison L, Pickard DJ, Martin MJ, Connor TR, Harris SR, Fairley D, Bamford KB, et al (2012). Emergence and global spread of epidemic healthcare-associated Clostridium difficile. Nature Genetics
Foster JAH, Butt JEC, Bell J, Goff A, Morgan C, Hancock J, Carmichael C, Keedwell EC, Michell SLI, Sheridan RP, et al (2012). IMPROVING CLINICAL MANAGEMENT IN CLOSTRIDIUM DIFFICILE: FAECAL CALPROTECTIN DOES NOT PREDICT SEVERITY, RECURRENCE OR MORTALITY. AGE AND AGEING, 41, 72-72.  Author URL.
Thomas RM, Twine SM, Fulton KM, Tessier L, Kilmury SLN, Ding W, Harmer N, Michell SL, Oyston PCF, Titball RW, et al (2011). Glycosylation of DsbA in Francisella tularensis subsp. tularensis. J Bacteriol, 193(19), 5498-5509. Abstract.  Author URL.
Kovacs-Simon A, Titball RW, Michell SL (2011). Lipoproteins of bacterial pathogens. Infect Immun, 79(2), 548-561. Abstract.  Author URL.
Wand ME, Müller CM, Titball RW, Michell SL (2011). Macrophage and Galleria mellonella infection models reflect the virulence of naturally occurring isolates of B. pseudomallei, B. thailandensis and B. oklahomensis. BMC Microbiol, 11(1). Abstract.  Author URL.
Wang W, Hale C, Goulding D, Haslam SM, Tissot B, Lindsay C, Michell S, Titball R, Yu J, Toribio AL, et al (2011). Mannosidase 2, alpha 1 deficiency is associated with ricin resistance in embryonic stem (ES) cells. PLoS One, 6(8). Abstract.  Author URL.
Vanaporn M, Wand M, Michell SL, Sarkar-Tyson M, Ireland P, Goldman S, Kewcharoenwong C, Rinchai D, Lertmemongkolchai G, Titball RW, et al (2011). Superoxide dismutase C is required for intracellular survival and virulence of Burkholderia pseudomallei. Microbiology (Reading), 157(Pt 8), 2392-2400. Abstract.  Author URL.
Michell SL, Dean RE, Eyles JE, Hartley MG, Waters E, Prior JL, Titball RW, Oyston PCF (2010). Deletion of the Bacillus anthracis capB homologue in Francisella tularensis subspecies tularensis generates an attenuated strain that protects mice against virulent tularaemia. J Med Microbiol, 59(Pt 11), 1275-1284. Abstract.  Author URL.
Forslund A-L, Salomonsson EN, Golovliov I, Kuoppa K, Michell S, Titball R, Oyston P, Noppa L, Sjöstedt A, Forsberg A, et al (2010). The type IV pilin, PilA, is required for full virulence of Francisella tularensis subspecies tularensis. BMC Microbiol, 10 Abstract.  Author URL.
Champion MD, Zeng Q, Nix EB, Nano FE, Keim P, Kodira CD, Borowsky M, Young S, Koehrsen M, Engels R, et al (2009). Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies. PLoS Pathog, 5(5). Abstract.  Author URL.
Richards MI, Michell SL, Oyston PCF (2008). An intracellularly inducible gene involved in virulence and polyphosphate production in Francisella. J Med Microbiol, 57(Pt 10), 1183-1192. Abstract.  Author URL.
Michell, S.L. Diaper, H. Wikstrom, P. Titball, RW (2007). A 55 kDa hypothetical membrane protein is an iron-regulated virulence factor of Francisella tularensis subspecies novicida U112. Journal of Medical Microbiology, 56, 1268-1276.
Isherwood, K.E. Michell, S.L. Diaper, H. Titball, RW (2007). A Francisella tularensis subspecies novicida purF mutant, but not a purA mutant, induces protective immunity to tularemia in mice. Vaccine, 25, 2011-2018.
sm202, Grice ID, Griffin K, Hitchen PG (2007). The immunologically distinct O-antigens from Francisella tularensis subspecies tuarensis and Francisella novicida are both virulence determinants and protective antigens. Infection and Immunity, 75(1), 371-378.
sm202, Bystrom A, Forslund AL, Johansson A (2006). Direct repeat-mediated deletion of a type IV pilin gene results in major virulence attenuation of Francisella tularensis. Molecular Microbiology, 59(6), 1818-1830.
RT101, Andersson SGE, Chain P, Chu MC (2005). The complete genome sequence of Francisella tularensis, the causative agent of tularemia. Nature Genetics, 37(2), 153-159.
Michell SL, Whelan AO, Wheeler PR, Panico M, Easton RL, Etienne AT, Haslam SM, Dell A, Morris HR, Reason AJ, et al (2003). The MPB83 antigen from Mycobacterium bovis contains O-linked mannose and (1->3)-mannibiose moieties. Journal of Biological Chemistry, 278(18), 16423-16432.
Wooff EE, Michell SL, Gordon SV, Chambers MA, Bardarov A, Jacobs Jr WR, Hewinson RG, Wheeler PR (2002). Functional genomics reveals the sole sulphate transporter of the mycobacterium tuberculosis complex and its relevance to the acquisition of sulphate in vivo. Molecular Microbiology, 43(3), 653-663.
Wiker HG, Michell SL, Hewinson RG, Spierings E, Nagai S, Harboe M (1999). Cloning, expression and significance of MPT53 for identification of secreted proteins of Mycobacterium tuberculosis. Microbial Pathogenesis, 26(4), 207-219. Abstract.
Hewinson RG, Michell SL, Russell WP, McAdam RA, Jacobs WR (1996). Molecular characterization of MPT83: a seroreactive antigen of Mycobacterium tuberculosis with homology to MPT70. Scand J Immunol, 43(5), 490-499. Abstract.  Author URL.

Chapters

Michell SL, Griffin, K.F. Titball, R.W. (2006). Tularemia Pathogenesis and Immunity. In Friedman H, Anderson B (Eds.) Microbial Infection and Bioterrorism, Kluwer Academic Publishers, 121-138.

Conferences

Fraser D, Keedwell EC, Michell S, Sheridan R (2019). EMOCS: Evolutionary Multi-objective Optimisation for Clinical Scorecard Generation. Genetic and Evolutionary Computation Conference, GECCO 2019. 13th - 17th Jul 2019.

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External Engagement and Impact

Committee/panel activities

Member of Prokaryotic Division, Microbiology Society. 2014- 2018

Advisor to DTI on the export of Biological Agents


Editorial responsibilities

Section Editor of Journal of Medical Microbiology 2018 - current 

Member of the Editorial board of Frontiers in Microbial Physiology and Metabolism 


Invited lectures

2016: XIII Congress of the Federazione Italiana Scienze della Vita, Rome

January 2012: Seminar at the University of Milan 20th Jan 2012

March 2004:  Laboratoire de Microbiologie et Genetique Moleculaires du CNRS, Universite Paul Sabatier, Toulouse Scientific Seminar Program

May 2001: Albert Einstein College of Medicine, Yeshiva University New York, Department of Microbiology and Immunology Scientific Seminar Program


Media Coverage

Scientists launch a new study into C-diff treatment (Western Morning News)

C. diff test to predict patients most at risk (BBC)

Life saving test (BBC Spotlight video)

Exeter University and Newton Abbot College join the fight against bacterial resistance (Exeter Express and Echo)

Scientists launch a new study into C-diff treatment (This is Devon)

COVID-19 Vaccine: Ask the Experts Q&A (119) COVID-19 Vaccine: Ask the Experts Q&A (recorded live 17th Dec 2020) - YouTube


Workshops/Conferences organised

 Member of the organising committee of the  South West and South Wales Microbiology Forum 2009

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Teaching

I contribute  to the 1st year module, Microbiology (BIO1337), and I am  the co-ordinator of the 3rd year module, Microbial Effectors of disease (BIO3079).

Modules

2023/24


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Supervision / Group

Postdoctoral researchers

  • Julie Fletcher
  • Robyn Manley

Postgraduate researchers

  • Jake Bowley
  • Christian Fitch
  • Alex Hughes
  • Gino Schiano Di Visconte
  • Beth Tindall-Jones

Alumni

  • Dr Emma Butt
  • Dr Selina Church
  • Edward Farries
  • Cameron Hubert
  • Andrea Kovacs-Simon
  • Dr Matthew Wand

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Office Hours:

9.30 to 10.30 Mondays

1.30 to 2.30 Wednesdays

2.30 to 3.30 Fridays

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