Dr Sarah Coulthurst
Overall my research aims to elucidate how Gram-negative bacterial pathogens are able to cause disease. This should provide both an improved understanding of basic biological processes and, ultimately, contribute to novel therapeutic antimicrobial strategies.
More specifically, I am interested in several inter-linked research areas:
1. Protein secretion
Currently I am primarily interested in the Type VI Secretion system. However I also have past and present interest in other secretion systems, especially Type II and Type I secretion systems.
2. Bacterial-bacterial interaction and regulation of virulence factor production
This includes production of secondary metabolites, such as antibiotics, quorum sensing and other global regulation systems.
3. Use of model systems and ‘omic’ approaches to elucidate bacterial-host and inter-bacterial interaction
Including non-mammalian virulence models, proteomics and whole-genome analyses
All together, these contribute towards a better understanding of how Gram-negative bacterial pathogens interact with the host organism and cause disease, how they interact with the environment and other bacteria, and how they co-ordinate the complex processes involved in virulence.
We study several Gram-negative bacterial pathogens, generally enteric, including the human pathogens Serratia marcescens, Enterobacter, and E. coli and the plant pathogens Erwinia spp. Overall we are a molecular microbiology group, utilising a variety of approaches from genetics, molecular biology and classical microbiology, through to biochemistry, proteomics and cell biology.
BI40051 - 4A05 Bacterial Membrane Biology
Cianfanelli, F. R., Alcoforado Diniz, J., Guo, M., De Cesare, V., Trost, M. and Coulthurst, S. J. (2016) VgrG and PAAR Proteins Define Distinct Versions of a Functional Type VI Secretion System. PLoS pathogens. 12, e1005735
Cianfanelli, F.R., Monlezun, L. & Coulthurst, S.J. (2016) Aim, Load, Fire: The Type VI Secretion System, a Bacterial Nanoweapon. Trends Microbiol, 24, 51-62.
Stanley-Wall, N.R., Coulthurst, S.J. & Holland, I.B. (2015) A Snapshot of the Extraordinary World of Social Microbiology. J Mol Biol, 427, 3625-7.
Alcoforado Diniz, J., Liu, Y. & Coulthurst, S.J. (2015) Molecular weaponry: diverse effectors delivered by the Type VI secretion system. Cell Microbiol, 17, 1742-51.
Gerc, A.J., Diepold, A., Trunk, K., Porter, M., Rickman, C., Armitage, J.P., Stanley-Wall, N.R. & Coulthurst, S.J. (2015) Visualization of the Serratia Type VI Secretion System Reveals Unprovoked Attacks and Dynamic Assembly. Cell Rep, 12, 2131-42.
Alcoforado Diniz, J. & Coulthurst, S.J. (2015) Intra-species Competition in Serratia marcescens is Mediated by Type VI-Secreted Rhs Effectors and a Conserved Effector-Associated Accessory Protein. J Bacteriol, 197, 2350-60.
Hamilton, J.J., Marlow, V.L., Owen, R.A., Costa, M.de A., Guo, M., Buchanan, G., Chandra, G., Trost, M., Coulthurst, S.J., Palmer, T., Stanley-Wall, N.R., & Sargent, F. (2014) A holin and an endopeptidase are essential for chitinolytic protein secretion in Serratia marcescens. J Cell Biol, 207, 615-26.
Iguchi, A., Komatsu, H., Nagaya, Y., Pradel, E., Ooka, T., Ogura, Y., Katsura, K., Kurokawa, K., Oshima, K., Hattori, M., Parkhill, J., Sebaihia, M., Coulthurst, S.J., Gotoh, N., Ewbank, J.E., Thomson, N.R. & Hayashi, T. (2014) Genome evolution and plasticity of Serratia marcescens, an important multidrug resistant nosocomial pathogen. Genome Biol Evol, 6, 2096-110.
Gerc A.J., Stanley-Wall N.R. & Coulthurst S.J. (2014) The role of the phosphopantetheinyl transferase enzyme, PswP, in the biosynthesis of antimicrobial secondary metabolites by Serratia marcescens Db10. Microbiology 160, 1609-17.
English G., Byron O., Cianfanelli F.R., Prescott A.R., & Coulthurst S.J. (2014) Biochemical analysis of TssK, a core component of the bacterial Type VI secretion system, reveals distinct oligomeric states of TssK and identifies a TssK-TssFG subcomplex. Biochem J, 461, 291-304.
Caly, D.L., Coulthurst, S.J., An, S.Q., Helaine, S., Malone, J.G., Ryan, R.P. (2014) Communication, Co-operation and Social Interactions: a report from the third 'Young Microbiologists Symposium on Microbe Signaling, Organization and Pathogenesis. J Bacteriol, 196, 3527-33.
Fritsch M.J., Trunk K., Alcoforado Diniz J., Guo M., Trost M. & Coulthurst, S.J. (2013) Proteomic identification of novel secreted anti-bacterial toxins of the Serratia marcescens Type VI secretion system. Mol Cell Proteomics, 12, 2735-49.
Srikannathasan V., English G., Bui, N.K., Trunk K., O’Rourke P.E.F., Rao V.A., Vollmer W., Coulthurst S.J. & Hunter W.N. (2013) Structural basis for Type VI secreted peptidoglycan DL-endopeptidase function, specificity and neutralization in Serratia marcescens. Acta Crystallogr D, 69, 2468-82.
James, M.J., Coulthurst, S.J., Palmer, T. & Sargent, F. (2013) Signal peptide etiquette during assembly of a complex respiratory enzyme. Mol Microbiol, 90, 400-14.
Coulthurst, S.J. (2013) The Type VI secretion system - a widespread and versatile cell targeting system. Res Microbiol, 164, 640-54.
Sargent, F., Davidson, F.A., Kelly, C.L., Binny, R., Christodoulides, N., Gibson, D., Johansson, E., Kozyrska, K., Lado, L.L., Maccallum, J., Montague, R., Ortmann, B., Owen, R., Coulthurst, S.J., Dupuy, L., Prescott, A.R. & Palmer, T. (2013) A synthetic system for expression of components of a bacterial microcompartment. Microbiology, 159, 2427-36.
English, G., Trunk, K., Rao, V.A., Srikannathasan, V., Hunter, W.N. & Coulthurst, S.J. (2012) New Secreted Toxins and Immunity Proteins Encoded within the Type VI Secretion System Gene Cluster of Serratia marcescens. Mol Microbiol, 86, 921-936.
Gerc, A.J., Song, L., Challis, G.L., Stanley-Wall, N.R. & Coulthurst, S.J. (2012) The insect pathogen Serratia marcescens Db10 uses a hybrid non-ribosomal peptide synthetase-polyketide synthase to produce the antibiotic althiomycin. PLoS One, 7:e44673.
Coulthurst, S.J., Dawson, A., Hunter, W.N. & Sargent, F. (2012) Conserved signal peptide recognition systems across the prokaryotic domains. Biochemistry, 51, 1678-86.
Lossi, N.S., Manoli, E., Simpson, P., Jones, C., Hui, K., Dajani, R., Coulthurst, S.J., Freemont, P. & Filloux, A. (2012) The archetype Pseudomonas aeruginosa proteins TssB and TagJ form a novel sub-complex in the bacterial Type VI secretion system. Mol Microbiol, 86, 437-56
Caly, D.L., Coulthurst, S.J., Geoghegan, J.A., Malone, J.G. & Ryan, R.P. (2012) Socializing, networking and development: a report from the second 'Young Microbiologists Symposium on Microbe Signalling, Organization and Pathogenesis'. Mol Microbiol, 86, 501-12.
Murdoch, S.L., Trunk, K., English, G., Fritsch, M.J., Pourkarimi, E. & Coulthurst, S.J. (2011) The opportunistic pathogen Serratia marcescens utilises Type VI Secretion to target bacterial competitors. J Bacteriol, 193, 6057-69.
Rao, V.A., Shepherd, S.M., English, G., Coulthurst, S.J. & Hunter, W.N. (2011) The structure of Serratia marcescens Lip; a membrane bound component of the Type VI secretion system. Acta Crystallogr D Biol Crystallogr, 67, 1065-1072.
Pérez-Mendoza, D., Coulthurst, S.J., Humphris, S., Campbell, E., Welch, M., Toth, I.K. & Salmond, G.P.C. (2011) A multi-repeat adhesin of the phytopathogen, Pectobacterium atrosepticum, is secreted by a Type I pathway and is subject to complex regulation involving a non-canonical diguanylate cyclase. Mol Microbiol 82, 719-33.