Dr Robert Fagan

School of Biosciences

Senior Lecturer

r.fagan@sheffield.ac.uk
+44 114 222 4182

Firth Court

Full contact details

Dr Robert Fagan
School of Biosciences
Firth Court
Western Bank
Sheffield
S10 2TN

Profile

Career history

2018-present: Senior Lecturer, School of Biosciences, University of Sheffield, UK
2013 - 2017: Lecturer, Dept. of Molecular Biology and Biotechnology, University of Sheffield, UK
2008 - 2012: Senior Research Associate, Centre for Molecular Microbiology and Infection, Imperial College London, UK
2005 - 2008: Research Associate, Centre for Molecular Microbiology and Infection, Imperial College London, UK
2001 - 2005: PhD, Moyne Institute of Preventive Medicine, Trinity College, University of Dublin, Ireland

Research interests

Clostridium difficile is the most common cause of antibiotic-associated diarrhea. It’s a highly antibiotic resistant pathogen that can cause severe disease following antibiotic-mediated disruption of the protective gut microbiota.

The aim of our research is to understand the molecular basis of interactions between the bacterium and its host. We study the outermost layer of the C. difficile cell envelope, the surface- or S-layer, a 2-dimensional proteinaceous crystal that completely coats the surface of the bacterium.

The S-layer has been implicated in adhesion and induction of innate immunity. Our work combines molecular microbiology and structural biology to study S-layer biogenesis and function.

Publications

Show: Featured publications All publications

Featured publications

Journal articles

Buddle JE, Thompson LM, Williams AS, Wright RCT, Durham WM, Turner CE, Chaudhuri RR, Brockhurst MA & Fagan RP (2024) Identification of pathways to high-level vancomycin resistance in Clostridioides difficile that incur high fitness costs in key pathogenicity traits. PLOS Biology, 22(8). View this article in WRRO
Lanzoni-Mangutchi P, Banerji O, Wilson J, Barwinska-Sendra A, Kirk JA, Vaz F, O'Beirne S, Baslé A, El Omari K, Wagner A , Fairweather NF et al (2022) Structure and assembly of the S-layer in C. difficile.. Nat Commun, 13(1), 970.
Fuchs M, Lamm-Schmidt V, Sulzer J, Ponath F, Jenniches L, Kirk JA, Fagan RP, Barquist L, Vogel J & Faber F (2021) An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium. Proceedings of the National Academy of Sciences of the United States of America, 118(25).
Kirk JA, Gebhart D, Buckley AM, Lok S, Scholl D, Douce GR, Govoni GR & Fagan RP (2017) New class of precision antimicrobials redefines role of Clostridium difficile S-layer in virulence and viability. Science Translational Medicine, 9(406).
Dembek M, Barquist L, Boinett CJ, Cain AK, Mayho M, Lawley TD, Fairweather NF & Fagan RP (2015) High-Throughput Analysis of Gene Essentiality and Sporulation in Clostridium difficile. MBIO, 6(2).

All publications

Journal articles

Wilson JS, Fortier L-C, Fagan RP & Bullough PA (2025) Molecular mechanism of bacteriophage contraction structure of an S-layer–penetrating bacteriophage. Life Science Alliance, 8(6). View this article in WRRO
Buddle JE, Thompson LM, Williams AS, Wright RCT, Durham WM, Turner CE, Chaudhuri RR, Brockhurst MA & Fagan RP (2024) Identification of pathways to high-level vancomycin resistance in Clostridioides difficile that incur high fitness costs in key pathogenicity traits. PLOS Biology, 22(8). View this article in WRRO
Galley NF, Greetham D, Alamán-Zárate MG, Williamson MP, Evans CA, Spittal WD, Buddle JE, Freeman J, Davis GL, Dickman MJ , Wilcox MH et al (2024) Clostridioides difficile canonical L,D-transpeptidases catalyze a novel type of peptidoglycan cross-links and are not required for beta-lactam resistance. Journal of Biological Chemistry, 300(1). View this article in WRRO
Phothichaisri W, Phetruen T, Chankhamhaengdecha S, Janvilisri T, Ounjai P, Fagan RP & Chanarat S (2024) Unraveling Physical Interactions of Clostridioides difficile with Phage and Phage-Derived Proteins Using In Vitro and Whole-Cell Assays, 245-262.
Ormsby MJ, Vaz F, Kirk JA, Barwinska-Sendra A, Hallam JC, Lanzoni-Mangutchi P, Cole J, Chaudhuri RR, Salgado PS, Fagan RP & Douce GR (2023) An intact S-layer is advantageous to Clostridioides difficile within the host. PLOS Pathogens, 19(6). View this article in WRRO
Royer ALM, Umansky AA, Allen M-M, Garneau JR, Ospina-Bedoya M, Kirk JA, Govoni G, Fagan RP, Soutourina O & Fortier L-C (2023) Clostridioides difficile S-Layer Protein A (SlpA) Serves as a General Phage Receptor.. Microbiol Spectr, 11(2), e0389422.
Buddle JE & Fagan RP (2023) Pathogenicity and virulence of Clostridioides difficile.. Virulence, 14(1), 2150452.
Phothichaisri W, Chankhamhaengdecha S, Janvilisri T, Nuadthaisong J, Phetruen T, Fagan RP & Chanarat S (2022) Potential Role of the Host-Derived Cell-Wall Binding Domain of Endolysin CD16/50L as a Molecular Anchor in Preservation of Uninfected Clostridioides difficile for New Rounds of Phage Infection.. Microbiol Spectr, 10(2), e0236121.
Lanzoni-Mangutchi P, Banerji O, Wilson J, Barwinska-Sendra A, Kirk JA, Vaz F, O'Beirne S, Baslé A, El Omari K, Wagner A , Fairweather NF et al (2022) Structure and assembly of the S-layer in C. difficile.. Nat Commun, 13(1), 970.
Alabdali YAJ, Oatley P, Kirk JA & Fagan RP (2021) A cortex-specific penicillin-binding protein contributes to heat resistance in Clostridioides difficile spores. Anaerobe, 70.
Fuchs M, Lamm-Schmidt V, Sulzer J, Ponath F, Jenniches L, Kirk JA, Fagan RP, Barquist L, Vogel J & Faber F (2021) An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium. Proceedings of the National Academy of Sciences of the United States of America, 118(25).
Oatley P, Kirk JA, Ma S, Jones S & Fagan RP (2020) Spatial organization of Clostridium difficile S-layer biogenesis. Scientific Reports, 10(1).
Janganan TK, Mullin N, Dafis-Sagarmendi A, Brunt J, Tzokov SB, Stringer S, Moir A, Chaudhuri RR, Fagan RP, Hobbs JK & Bullougha PA (2020) Architecture and self-assembly of clostridium sporogenes and clostridium botulinum spore surfaces illustrate a general protective strategy across spore formers. Msphere, 5(4).
de Lussy-Kubisa L, Chaudhuri R & Fagan R (2019) Applying transposon-directed insertion site sequencing to industrially important, solventogenic species Clostridium saccharoperbutylacetonicum. Access Microbiology, 1(1A).
Vaz F, Wilson G, Kirk J, Salgado P, Fagan R & Douce G (2019) Unraveling the role of C. difficile S-layer in infection and disease. Access Microbiology, 1(1A).
O’Beirne S, Kirk JA & Fagan RP (2019) Clostridium difficile: cell surface biogenesis. Access Microbiology, 1(1A).
Fagan R, McBride SM & Shen A (2018) Editorial. Anaerobe, 53, 1-1.
McHale TM, Garciarena CD, Fagan RP, Smith SGJ, Martin-Loches I, Curley GF, Fitzpatrick F & Kerrigan SW (2018) Inhibition of Vascular Endothelial Cell Leak Following Escherichia coli Attachment in an Experimental Model of Sepsis. Critical Care Medicine, 46(8), E805-E810.
Kirk JA, Gebhart D, Buckley AM, Lok S, Scholl D, Douce GR, Govoni GR & Fagan RP (2017) New class of precision antimicrobials redefines role of Clostridium difficile S-layer in virulence and viability. Science Translational Medicine, 9(406).
Kirk JA, Banerji O & Fagan RP (2017) Characteristics of the Clostridium difficile cell envelope and its importance in therapeutics. Microbial Biotechnology, 10(1), 76-90.
Kirk JA & Fagan RP (2016) Heat shock increases conjugation efficiency in Clostridium difficile. Anaerobe, 42, 1-5.
Buckley AM, Jukes C, Candlish D, Irvine JJ, Spencer J, Fagan RP, Roe AJ, Christie JM, Fairweather NF & Douce GR (2016) Lighting Up Clostridium Difficile: Reporting Gene Expression Using Fluorescent Lov Domains. Scientific Reports, 6.
Willing SE, Candela T, Shaw HA, Seager Z, Mesnage S, Fagan RP & Fairweather NF (2015) Clostridium difficile surface proteins are anchored to the cell wall using CWB2 motifs that recognise the anionic polymer PSII. Molecular Microbiology, 96(3), 596-608.
Dembek M, Barquist L, Boinett CJ, Cain AK, Mayho M, Lawley TD, Fairweather NF & Fagan RP (2015) High-Throughput Analysis of Gene Essentiality and Sporulation in Clostridium difficile. MBIO, 6(2).
Pettit LJ, Browne HP, Yu L, Smits WK, Fagan RP, Barquist L, Martin MJ, Goulding D, Duncan SH, Flint HJ , Dougan G et al (2014) Functional genomics reveals that Clostridium difficile Spo0A coordinates sporulation, virulence and metabolism. BMC Genomics, 15(1).
Fagan RP & Fairweather NF (2014) Biogenesis and functions of bacterial S-layers. Nature Reviews Microbiology, 12(3), 211-222.
Deakin LJ, Clare S, Fagan RP, Dawson LF, Pickard DJ, West MR, Wren BW, Fairweather NF, Dougan G & Lawley TD (2012) The Clostridium difficile spo0A gene is a persistence and transmission factor.. Infect Immun, 80(8), 2704-2711.
Mahon V, Fagan RP & Smith SGJ (2012) Snap denaturation reveals dimerization by AraC-like protein Rns. Biochimie, 94(9), 2058-2061.
Tam Dang TH, Fagan RP, Fairweather NF & Tate EW (2012) Novel inhibitors of surface layer processing in Clostridium difficile.. Bioorg Med Chem, 20(2), 614-621.
Fagan RP & Fairweather NF (2011) Clostridium difficile has two parallel and essential Sec secretion systems.. J Biol Chem, 286(31), 27483-27493.
Reynolds CB, Emerson JE, de la Riva L, Fagan RP & Fairweather NF (2011) The Clostridium difficile cell wall protein CwpV is antigenically variable between strains, but exhibits conserved aggregation-promoting function.. PLoS Pathog, 7(4), e1002024.
Fagan RP, Janoir C, Collignon A, Mastrantonio P, Poxton IR & Fairweather NF (2011) A proposed nomenclature for cell wall proteins of Clostridium difficile.. J Med Microbiol, 60(Pt 8), 1225-1228.
Fagan R & Fairweather N (2010) Dissecting the cell surface.. Methods Mol Biol, 646, 117-134.
Dang THT, de la Riva L, Fagan RP, Storck EM, Heal WP, Janoir C, Fairweather NF & Tate EW (2010) Chemical probes of surface layer biogenesis in Clostridium difficile.. ACS Chem Biol, 5(3), 279-285.
Emerson JE, Reynolds CB, Fagan RP, Shaw HA, Goulding D & Fairweather NF (2009) A novel genetic switch controls phase variable expression of CwpV, a Clostridium difficile cell wall protein.. Mol Microbiol, 74(3), 541-556.
Fagan RP, Albesa-Jové D, Qazi O, Svergun DI, Brown KA & Fairweather NF (2009) Structural insights into the molecular organization of the S-layer from Clostridium difficile.. Mol Microbiol, 71(5), 1308-1322.
Fagan RP, Lambert MA & Smith SGJ (2008) The hek outer membrane protein of Escherichia coli strain RS218 binds to proteoglycan and utilizes a single extracellular loop for adherence, invasion, and autoaggregation.. Infect Immun, 76(3), 1135-1142.
Smith SGJ, Mahon V, Lambert MA & Fagan RP (2007) A molecular Swiss army knife: OmpA structure, function and expression.. FEMS Microbiol Lett, 273(1), 1-11.
Fagan RP & Smith SGJ (2007) The Hek outer membrane protein of Escherichia coli is an auto-aggregating adhesin and invasin.. FEMS Microbiol Lett, 269(2), 248-255.
Janganan TK, Mullin N, Tzokov SB, Stringer S, Fagan RP, Hobbs JK, Moir A & Bullough PA () Characterization of the spore surface and exosporium proteins of Clostridium sporogenes; implications for C. botulinum Group I strains. Food Microbiology, 59, 205-212. View this article in WRRO

Preprints

Buddle JE, Pennington VK, Kirk JA, Faber F, Turner CE, Brockhurst MA & Fagan RP (2025) A novel two-component system controls vancomycin resistance in epidemic Clostridioides difficile, Cold Spring Harbor Laboratory.
Janganan TK, Mullin N, Dafis-Sagarmendi A, Brunt J, Tzokov SB, Stringer S, Moir A, Chaudhuri R, Fagan RP, Hobbs JK & Bullough PA (2020) Architecture and self-assembly of theClostridium sporogenes/botulinumspore surface illustrate a general protective strategy across spore formers, Cold Spring Harbor Laboratory.
Oatley P, Kirk J, Ma S, Jones S & Fagan R (2018) Spatial organization of Clostridium difficile S-layer biogenesis.

Teaching activities

Level 3 modules

MBB328 The Organisation of Bacterial Cells (Module Coordinator)
MBB335 Bacterial Pathogenicity (Module Coordinator)