Mesnage, Stéphane, Dr

Dr Stéphane Mesnage

School of Biosciences

Senior Lecturer

s.mesnage@sheffield.ac.uk
+44 114 222 4405

Firth Court

Full contact details

Dr Stéphane Mesnage
School of Biosciences
Firth Court
Western Bank
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S10 2TN

Profile

2019 - present: Senior Lecturer, School of Biosciences, University of ��«Ӱҵ, UK
2012 - 2018: Lecturer, Dept. of Molecular Biology and Biotechnology, University of ��«Ӱҵ, UK
2010 - 2012: Marie Curie (IEF) Fellow, Dept. of Molecular Biology and Biotechnology, University of ��«Ӱҵ, UK
2002 - 2010: INSERM Chargé de Recherches, University of Paris 6, France
2000 - 2002: EMBO Research assistant, John Innes Centre, Norwich, UK
1996 - 2000: PhD, Pasteur Institute, Paris, France

Research interests

My work is focused on the study of the bacterial cell wall using essentially two Gram-positive pathogens (Staphylococcus aureus, Enterococcus faecalis) as models. I am interested in three major areas of research.

Analysis of protein-cell wall interactions

The essential cell wall peptidoglycan polymer network forms a scaffold for the display of a large variety of proteins involved in cell division, metabolism, cell-cell communication and in pathogen interaction with the host. Although several multimodular cell wall binding domains have been identified to date in bacteria, both their structural organisation and binding mechanism (binding motif, subcellular localisation) have remained elusive.

The aim of this project is to understand the molecular mechanisms underpinning protein-bacterial cell wall interactions and subcellular localisation of surface proteins.

Beyond these fundamental questions, the aim is to develop a translational research program to (i) develop peptidoglycan binding domains as new functional probes to provide a nanoscale topological map of the cell surface; (ii) provide an experimental rationale to engineer and target therapeutic molecules against pathogens.

This project involves multidisciplinary approaches across several disciplines including molecular biology, biochemistry, biophysics, structural biology and state-of-the-art super resolution microscopy.

Control of peptidoglycan hydrolysis during growth

During growth, the insertion of new precursors and separation of daughter cells requires limited cleavage of the peptidoglycan molecule by peptidoglycan hydrolases.

Depending on the bond they cleave, these enzymes are classified as N-acetylmuramidases, N-acetylglucosaminidases, N-acetylmuramoyl L-alanine amidases, endopeptidases or carboxypeptidases (Fig. 2). In addition to their contribution to cell growth and division, some peptidoglycan hydrolases play a role in adhesion and in amplification of the inflammatory response by releasing muramyl-peptides.

The lytic activity of some peptidoglycan hydrolases (called autolysins) is potentially lethal and can lead to cell lysis and death. How bacteria control autolytic activities is poorly understood.

I am studying several mechanisms that may be responsible for the control of autolytic activities: (i) the subcellular targeting of autolysins; (ii) the impact of peptidoglycan structural properties on autolytic activities and (iii) the contribution of the electrochemical gradient across the cytoplasmic membrane to the control of peptidoglycan hydrolysis.

We routinely analyse peptidoglycan hydrolase substrate specificity by a combination of rp-HPLC and mass spectrometry. The enzymatic activity of autolysins is measured spectrophotometrically.

Role of Enterococcus faecalis cell wall metabolism in the interaction with the host

Lysozyme is the major component of the innate immune system and represents the first line of defense against pathogens. E. faecalis is highly resistant to lysozyme, with a minimal inhibitory concentration (MIC) above 50 mg/ml.

This extreme resistance has been partly explained by an additive effect of peptidoglycan O-acetylation and de-N-acetylation, as well as teichoic acid D-alanylation. It was also shown that full lysozyme resistance requires a signalling cascade involving the extracytoplasm

ic function (ECF) sigma factor SigV. Interestingly, E. faecalis strains harbouring multiple deletions in these pathways are still resistant to lysozyme. The identification of novel factors involved in lysozyme resistance is currently underway using random transposon mutagenesis. The mutants isolated will be further characterised in vivo.

Publications

Show: Featured publications All publications

Featured publications

Journal articles

Salamaga B, Prajsnar TK, Jareño-Martinez A, Willemse J, Bewley MA, Chau F, Ben Belkacem T, Meijer AH, Dockrell DH, Renshaw SA & Mesnage S (2017) . PLoS Pathogens, 13(7).
Mesnage S, Dellarole M, Baxter NJ, Rouget J-B, Dimitrov JD, Wang N, Fujimoto Y, Hounslow AM, Lacroix-Desmazes S, Fukase K , Foster SJ et al (2014) . Nat Commun, 5, 4269.
Prajsnar TK, Renshaw SA, Ogryzko NV, Foster SJ, Serror P & Mesnage S (2013) . Infect Immun, 81(11), 4271-4279.
Wheeler R, Mesnage S, Boneca IG, Hobbs JK & Foster SJ (2011) . Molecular Microbiology, 82(5), 1096-1109.
de Roca FR, Duché C, Dong S, Rincé A, Dubost L, Pritchard DG, Baker JR, Arthur M & Mesnage S (2010) . J Mol Biol, 398(4), 507-517.
Emirian A, Fromentin S, Eckert C, Chau F, Dubost L, Delepierre M, Gutmann L, Arthur M & Mesnage S (2009) . FEBS Lett, 583(18), 3033-3038.
Mesnage S, Chau F, Dubost L & Arthur M (2008) . J Biol Chem, 283(28), 19845-19853.

All publications

Journal articles

Davis JL, Norwood JS, Smith RE, O'Dea F, Chellappa K, Rowe ML, Williamson MP, Stafford GP, Vinogradov E, Maes E , Guérardel Y et al (2025) . Carbohydrate Polymers, 347, 122686-122686.
Alrafaie AM, Pyrzanowska K, Smith EM, Partridge DG, Rafferty J, Mesnage S, Shepherd J & Stafford GP (2024) . Virus Research, 347, 199426-199426.
Davis JL, Norwood JS, Smith RE, O'Dea F, Chellappa K, Rowe ML, Williamson MP, Stafford GP, Vinogradov E, Maes E , Guérardel Y et al (2024) . Carbohydrate Polymers, 122983-122983.
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 (2023) . Journal of Biological Chemistry, 105529-105529.
Alaman-Zarate MG, Rady BJ, Evans CA, Pian B, Greetham D, Marecos-Ortiz S, Dickman MJ, Lidbury IDEA, Lovering AL, Barstow BM & Mesnage S (2023) . Journal of Biological Chemistry, 105494-105494.
Salamaga B, Turner RD, Elsarmane F, Galley NF, Kulakauskas S & Mesnage S (2023) . Communications Biology, 6(1).
Ledger EVK, Mesnage S & Edwards AM (2022) . Nature Communications, 13(1).
Zamboni V, Barelier S, Dixon R, Galley NF, Ghanem A, Nguyen QP, Cahuzac H, Salamaga B, Davis PJ, Bourne Y , Mesnage S et al (2022) . Journal of Biological Chemistry.
Małecki PH, Mitkowski P, Jagielska E, Trochimiak K, Mesnage S & Sabała I (2021) . International Journal of Molecular Sciences, 22(13).
Sibinelli-Sousa S, Hespanhol JT, Nicastro GG, Matsuyama BY, Mesnage S, Patel A, de Souza RF, Guzzo CR & Bayer-Santos E (2020) . Cell Reports, 31(12).
Guerardel Y, Sadovskaya I, Maes E, Furlan S, Chapot-Chartier M-P, Mesnage S, Rigottier-Gois L & Serror P (2020) . mBio, 11(2).
Gonzalez-Delgado LS, Walters-Morgan H, Salamaga B, Robertson AJ, Hounslow AM, Jagielska E, Sabała I, Williamson MP, Lovering AL & Mesnage S (2019) . Nature Chemical Biology.
Bublitz DC, Chadwick GL, Magyar JS, Sandoz KM, Brooks DM, Mesnage S, Ladinsky MS, Garber AI, Bjorkman PJ, Orphan VJ & McCutcheon JP (2019) . Cell, 179(3), 703-712.e7.
Al-Zubidi M, Widziolek M, Court EK, Gains AF, Smith RE, Ansbro K, Alrafaie A, Evans C, Murdoch C, Mesnage S , Douglas CWI et al (2019) . Infection and Immunity.
Smith RE, Salamaga B, Szkuta P, Hajdamowicz N, Prajsnar TK, Bulmer GS, Fontaine T, Kołodziejczyk J, Herry J-M, Hounslow AM , Williamson MP et al (2019) . PLOS Pathogens, 15(5).
Turner RD, Mesnage S, Hobbs JK & Foster SJ (2018) . Nature Communications, 9(1).
Lund VA, Wacnik K, Turner RD, Cotterell BE, Walther CG, Fenn SJ, Grein F, Wollman AJM, Leake MC, Olivier N , Cadby A et al (2018) . eLife, 7.
Zhang X, de Maat V, Guzmán Prieto AM, Prajsnar TK, Bayjanov JR, de Been M, Rogers MRC, Bonten MJM, Mesnage S, Willems RJL & van Schaik W (2017) . BMC Genomics, 18(1).
Salamaga B, Prajsnar TK, Jareño-Martinez A, Willemse J, Bewley MA, Chau F, Ben Belkacem T, Meijer AH, Dockrell DH, Renshaw SA & Mesnage S (2017) . PLoS Pathogens, 13(7).
Mihelič M, Vlahoviček-Kahlina K, Renko M, Mesnage S, Doberšek A, Taler-Verčič A, Jakas A & Turk D (2017) . IUCrJ, 4(Pt 2), 185-198.
Bern M, Beniston R & Mesnage S (2016) . Analytical and Bioanalytical Chemistry, 409(2), 551-560.
Rodríguez-Rubio L, Gerstmans H, Thorpe S, Mesnage S, Lavigne R & Briers Y (2016) . Applied and Environmental Microbiology, 82(16), 4975-4981.
Oliveira H, Vilas Boas D, Mesnage S, Kluskens LD, Lavigne R, Sillankorva S, Secundo F & Azeredo J (2016) . Frontiers in Microbiology, 7.
Wheeler R, Turner RD, Bailey RG, Salamaga B, Mesnage S, Mohamad SAS, Hayhurst EJ, Horsburgh M, Hobbs JK & Foster SJ (2015) . mBio, 6(4).
Willing SE, Candela T, Shaw HA, Seager Z, Mesnage S, Fagan RP & Fairweather NF (2015) . Molecular Microbiology, 96(3), 596-608.
Lowry RC, Parker JL, Kumbhar R, Mesnage S, Shaw JG & Stafford GP (2015) . MicrobiologyOpen, 4(2), 220-234.
Lecerf M, Scheel T, Pashov AD, Jarossay A, Ohayon D, Planchais C, Mesnage S, Berek C, Kaveri SV, Lacroix-Desmazes S & Dimitrov JD (2015) . Journal of Biological Chemistry, 290(8), 5203-5213.
Mesnage S, Dellarole M, Baxter NJ, Rouget J-B, Dimitrov JD, Wang N, Fujimoto Y, Hounslow AM, Lacroix-Desmazes S, Fukase K , Foster SJ et al (2014) . Nat Commun, 5, 4269.
Dimitrov JD, Planchais C, Scheel T, Ohayon D, Mesnage S, Berek C, Kaveri SV & Lacroix-Desmazes S (2014) . J Biol Chem, 289(25), 17767-17779.
Prajsnar TK, Renshaw SA, Ogryzko NV, Foster SJ, Serror P & Mesnage S (2013) . Infect Immun, 81(11), 4271-4279.
Veyrier FJ, Williams AH, Mesnage S, Schmitt C, Taha M-K & Boneca IG (2013) . Mol Microbiol, 87(5), 1100-1112.
Mesnage SA & Foster SJ (2013) , 1, 1401-1407.
Benachour A, Ladjouzi R, Le Jeune A, Hébert L, Thorpe S, Courtin P, Chapot-Chartier M-P, Prajsnar TK, Foster SJ & Mesnage S (2012) . J Bacteriol, 194(22), 6066-6073.
Wheeler R, Mesnage S, Boneca IG, Hobbs JK & Foster SJ (2011) . Molecular Microbiology, 82(5), 1096-1109.
Dubée V, Chau F, Arthur M, Garry L, Benadda S, Mesnage S, Lefort A & Fantin B (2011) . Antimicrob Agents Chemother, 55(2), 910-912.
de Roca FR, Duché C, Dong S, Rincé A, Dubost L, Pritchard DG, Baker JR, Arthur M & Mesnage S (2010) . J Mol Biol, 398(4), 507-517.
Emirian A, Fromentin S, Eckert C, Chau F, Dubost L, Delepierre M, Gutmann L, Arthur M & Mesnage S (2009) . FEBS Lett, 583(18), 3033-3038.
Bravetti A-L, Mesnage S, Lefort A, Chau F, Eckert C, Garry L, Arthur M & Fantin B (2009) . Antimicrob Agents Chemother, 53(4), 1667-1669.
Mesnage S, Chau F, Dubost L & Arthur M (2008) . J Biol Chem, 283(28), 19845-19853.
Villet R, Fonvielle M, Busca P, Chemama M, Maillard AP, Hugonnet J-E, Dubost L, Marie A, Josseaume N, Mesnage S , Mayer C et al (2007) . Nucleic Acids Res, 35(20), 6870-6883.
Eckert C, Magnet S & Mesnage S (2007) . FEBS Lett, 581(4), 693-696.
Eckert C, Lecerf M, Dubost L, Arthur M & Mesnage S (2006) . J Bacteriol, 188(24), 8513-8519.
Mylne JS, Barrett L, Tessadori F, Mesnage S, Johnson L, Bernatavichute YV, Jacobsen SE, Fransz P & Dean C (2006) . Proc Natl Acad Sci U S A, 103(13), 5012-5017.
Maillard AP, Biarrotte-Sorin S, Villet R, Mesnage S, Bouhss A, Sougakoff W, Mayer C & Arthur M (2005) . J Bacteriol, 187(11), 3833-3838.
Mignot T, Couture-Tosi E, Mesnage S, Mock M & Fouet A (2004) . Int J Med Microbiol, 293(7-8), 619-624.
Couture-Tosi E, Delacroix H, Mignot T, Mesnage S, Chami M, Fouet A & Mosser G (2002) . J Bacteriol, 184(23), 6448-6456.
Levy YY, Mesnage S, Mylne JS, Gendall AR & Dean C (2002) . Science, 297(5579), 243-246.
Mignot T, Mesnage S, Couture-Tosi E, Mock M & Fouet A (2002) . Mol Microbiol, 43(6), 1615-1627.
Fouet A & Mesnage S (2002) . Curr Top Microbiol Immunol, 271, 87-113.
Mesnage S & Fouet A (2002) . J Bacteriol, 184(1), 331-334.
Mesnage S, Haustant M & Fouet A (2001) . Microbiology, 147(Pt 5), 1343-1351.
Mesnage S (2001) Conserved anchoring mechanisms between crystalline cell surface S-layer proteins and secondary cell wall polymers in Gram-positive bacteria? Response. TRENDS MICROBIOL, 9(2), 49-50.
Mesnage S, Fontaine T, Mignot T, Delepierre M, Mock M & Fouet A (2000) . EMBO J, 19(17), 4473-4484.
Mesnage S, Weber-Levy M, Haustant M, Mock M & Fouet A (1999) . Infect Immun, 67(9), 4847-4850.
Fouet A, Mesnage S, Tosi-Couture E, Gounon P & Mock M (1999) . J Appl Microbiol, 87(2), 251-255.
Mesnage S, Tosi-Couture E, Mock M & Fouet A (1999) . J Appl Microbiol, 87(2), 256-260.
Mesnage S, Tosi-Couture E & Fouet A (1999) . Mol Microbiol, 31(3), 927-936.
Mesnage S, Tosi-Couture E, Gounon P, Mock M & Fouet A (1998) . J Bacteriol, 180(1), 52-58.
Bahl H, Scholz H, Bayan N, Chami M, Leblon G, Gulik-Krzywicki T, Shechter E, Fouet A, Mesnage S, Tosi-Couture E , Gounon P et al (1997) . FEMS Microbiology Reviews, 20(1-2), 47-98.
Bahl H, Scholz H, Bayan N, Chami M, Leblon G, Gulik-Krzywicki T, Shechter E, Fouet A, Mesnage S, Tosi-Couture E , Gounon P et al (1997) . FEMS Microbiol Rev, 20(1-2), 47-98.
Mesnage S, Tosi-Couture E, Mock M, Gounon P & Fouet A (1997) . Mol Microbiol, 23(6), 1147-1155.
el-Turk J, Asemota O, Leymarie J, Sallaud C, Mesnage S, Breda C, Buffard D, Kondorosi A & Esnault R (1996) . Gene, 170(2), 213-216.
Norwood JS, Davis JL, Salamaga B, Moss CE, Johnston SA, Elks PM, Kiss‐Toth E & Mesnage S () . Molecular Microbiology.
Sanz-Gaitero M, De Maesschalck V, Patel A, Longin H, Van Noort V, Rodriguez-Rubio L, van Ryne M, Danis-Wlodarczyk K, Drulis-Kawa Z, Mesnage S , van Raaij M et al () . PHAGE.
Davis JL, Hounslow AM, Baxter NJ, Mesnage S & Williamson MP () . Biomolecular NMR Assignments.
Sandoz KM, Moore RA, Beare PA, Patel AV, Smith RE, Bern M, Hwang H, Cooper CJ, Priola SA, Parks JM , Gumbart JC et al () . Nature Microbiology.
Patel AV, Turner RD, Rifflet A, Acosta-Martin AE, Nichols A, Awad MM, Lyras D, Gomperts Boneca I, Bern M, Collins MO & Mesnage S () . eLife, 10.

Chapters

Rady BJ & Mesnage S (2024) , Protein Bioinformatics (pp. 111-132). Springer US
Mesnage S & Foster SJ (2013) , Handbook of Proteolytic Enzymes (pp. 1401-1407). Elsevier

Conference proceedings papers

Davis J, Smith R, Maes E, Guerardel Y & Mesnage S (2022) Determining the structure of the enterococcal polysaccharide antigen. FEBS OPEN BIO, Vol. 12 (pp 41-41)
Hespanhol JT, Sibinelli-Souza S, Nicastro GG, Matsuyama BY, Mesnage S, Patel A, de Souza RF, Guzzo CR, Farah C & Bayer-Santos E (2021) A Family of T6SS Antibacterial Effectors related to L,D-transpeptidases Targets the Peptidoglycan. BIOPHYSICAL REVIEWS, Vol. 13(6) (pp 1408-1409)
Bern MW, Beniston R & Mesnage S (2016) Automated Analysis of Bacterial Peptidoglycan Structure. GLYCOBIOLOGY, Vol. 26(12) (pp 1457-1457)

Preprints

Smith RE, Christena RL, Michno BJ, Davis JL, Lidbury IDEA, Alaman-Zarate M, Stefanidi D, Maes E, Fisher H, Prajsnar TK & Mesnage S (2024) , Cold Spring Harbor Laboratory.
Davis JL, Norwood JS, Smith RE, O’Dea F, Chellappa K, Rowe ML, Williamson MP, Stafford GP, Vinogradov E, Maes E , Guérardel Y et al (2024) , Cold Spring Harbor Laboratory.
Norwood JS, Davis JL, Salamaga B, Moss CE, Johnston S, Elks PM, Kiss-Toth E & Mesnage S (2024) , Cold Spring Harbor Laboratory.
S JN, L JD, Salamaga B, E CM, Johnston SA, Elks PM, Kiss-Toth E & MESNAGE S (2024) , Authorea, Inc..
Alaman-Zarate MG, Rady BJ, Evans CA, Pian B, Greetham D, Marecos-Ortiz S, Dickman MJ, Lidbury IDEA, Lovering AL, Barstow BM & Mesnage S (2023) , Cold Spring Harbor Laboratory.
Ledger EVK, Mesnage S & Edwards AM () , Cold Spring Harbor Laboratory.
Patel AV, Turner RD, Rifflet A, Acosta-Martin AE, Nichols A, Awad MM, Lyras D, Gomperts-Boneca I, Bern M, Collins MO & Mesnage S () .
de Sousa SS, Hespanhol JT, Nicastro GG, Matsuyama BY, Mesnage S, Patel A, de Souza RF, Guzzo CR & Bayer-Santos E () , Cold Spring Harbor Laboratory.
Sibinelli-Sousa S, Hespanhol JT, Nicastro GG, Matsuyama BY, Mesnage S, Patel A, de Souza RF, Guzzo CR & Bayer Santos E () .
Smith RE, Salamaga B, Szkuta P, Hajdamowicz N, Prajsnar TK, Bulmer G, Fontaine T, Kołodziejczyk J, Herry J-M, Hounslow A , Williamson MP et al () , Cold Spring Harbor Laboratory.
Zhang X, Guzman Prieto AM, de Maat V, Prajsnar TK, Bayjanov JR, de Been M, Rogers MRC, Bonten MJM, Mesnage S, Willems RJL & van Schaik W () , Cold Spring Harbor Laboratory.

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School of Biosciences

School of Biosciences

Dr Stéphane Mesnage

Analysis of protein-cell wall interactions

Control of peptidoglycan hydrolysis during growth

Role of Enterococcus faecalis cell wall metabolism in the interaction with the host

Featured publications

Journal articles

All publications

Journal articles

Chapters

Conference proceedings papers

Preprints

Links