Dr Nick Waterfield
Profile
Current Research
It is only recently that the important relationship between pathogens of vertebrates and invertebrates has been appreciated. Conservation of key features of the innate immune responses of invertebrates such as insects, and mammals suggests that universal offensive strategies can be employed by bacterial pathogens of these two groups. This observation is vital to the understanding of the evolution of bacterial virulence as the innate response is arguably the most important aspect of immunity in all animals, including mammals. Given the age of the invertebrate lineages, the enormous number of different species and individuals, and the diversity of the lifestyles they employ it seems likely that they have provided both a reservoir and a vector for the flow of horizontally transferred virulence factors between pathogens of very different host organisms.
We argue that invertebrate pathogens provide a massive reservoir of bacterial pathogens that are “pre-adapted” to tackle a basic innate-immune response in man. The model organisms we use to investigate this situation are Bacillus cereus (progenitor of B. anthracis) and the emerging human pathogen Photorhabdus asymbiotica. The genus Photorhabdus are enterobacteriaceae that are symbiotically associated with entomopathogenic Heterorhabditid nematodes. The P. luminescens and P. temperata are restricted to insect hosts, while the P. asymbiotica can also cause a severe clinical infection.
Research projects
- Characterising the genes and processes important in insect and human pathogenic variants of Photorhabdus using a “systems biology” approach.
- Determining how certain strains of Bacillus cereus are adapting to mammalian virulence using insect infection models and tissue culture.
- Developing insect as alternatives to mammalian animal model infections using Pseudomonas, Staphylococcus, Burkholderia and Bacillus.
- Using Chemical and Genomic approaches to exploit secondary metabolite (“natural product”) diversity in insect associated bacteria
- The development of Biomemetic nanotechnology as responsive wound dressings
Publications
Freeman, Z. N., Dorus, S. and Waterfield, N. R., 2013. The KdpD/KdpE two-component system : integrating K+ homeostasis and virulence. PLoS Pathogens, 9 (3), e1003201.
Pereira Morais, M. P., Marshall, D., Flower, S. E., Caunt, C. J., James, T. D., Williams, R. J., Waterfield, N. R. and Van Den Elsen, J. M. H., 2013. Analysis of protein glycation using fluorescent phenylboronate gel electrophoresis. Scientific Reports, 3, 1437.
Beeton, M.L., Atkinson, D.J. and Waterfield, N.R., 2013. An amoeba phagocytosis model reveals a novel developmental switch in the insect pathogen Bacillus thuringiensis. Journal of Insect Physiology, 59 (2), pp. 223-231.
Thanwisai, A., Tandhavanant, S., Saiprom, N., Waterfield, N. R., Ke Long, P., Bode, H. B., Peacock, S. J. and Chantratita, N., 2012. Diversity of Xenorhabdus and Photorhabdus spp. and their symbiotic entomopathogenic nematodes from Thailand. PLoS ONE, 7 (9), e43835.
Yang, G., Hernández-Rodríguez, C.S., Beeton, M.L., Wilkinson, P., ffrench-Constant, R.H. and Waterfield, N. R., 2012. Pdl1 is a putative lipase that enhances Photorhabdus toxin complex secretion. PLoS Pathogens, 8 (5), e1002692.
Vlisidou, I., Waterfield, N. and Wood, W., 2012. Elucidating the in vivo targets of Photorhabdus toxins in real-time using Drosophila embryos. Advances in Experimental Medicine and Biology, 710, pp. 49-57.
Amos, M. R., Sanchez-Contreras, M., Jackson, R. W., Munoz-Berbel, X., Ciche, T. A., Yang, G., Cooper, R. M. and Waterfield, N. R., 2011. Influence of the Photorhabdus luminescens phosphomannose isomerase gene, manA, on mannose utilization, exopolysaccharide structure, and biofilm formation. Applied and Environmental Microbiology, 77 (3), pp. 776-785.
Poulter, N., Donaldson, M., Mulley, G., Duque, L., Waterfield, N., Shard, A. G., Spencer, S., Jenkins, A. T. A. and Johnson, A. L., 2011. Plasma deposited metal Schiff-base compounds as antimicrobials. New Journal of Chemistry, 35 (7), pp. 1477-1484.
Dowling, A. J., Wilkinson, P. A., Holden, M. T. G., Quail, M. A., Bentley, S. D., Reger, J., Waterfield, N. R., Titball, R. W. and Ffrench-Constant, R. H., 2010. Genome-Wide Analysis Reveals Loci Encoding Anti-Macrophage Factors in the Human Pathogen Burkholderia pseudomallei K96243. PLoS ONE, 5 (12), e15693.
Peat, S. M., Ffrench-Constant, R. H., Waterfield, N. R., Marokhazi, J., Fodor, A. and Adams, B. J., 2010. A robust phylogenetic framework for the bacterial genus Photorhabdus and its use in studying the evolution and maintenance of bioluminescence: A case for 16S, gyrB, and glnA. Molecular Phylogenetics and Evolution, 57 (2), pp. 728-740.
Vlisidou, I., Eleftherianos, I., Dorus, S., Yang, G., Ffrench-Constant, R. H., Reynolds, S. E. and Waterfield, N. R., 2010. The KdpD/KdpE two-component system of Photorhabdus asymbiotica promotes bacterial survival within M. sexta hemocytes. Journal of Invertebrate Pathology, 105 (3), pp. 352-362.
Wilkinson, P., Paszkiewicz, K., Moorhouse, A., Szubert, J. M., Beatson, S., Gerrard, J., Waterfield, N. R. and Ffrench-Constant, R. H., 2010. New plasmids and putative virulence factors from the draft genome of an Australian clinical isolate of Photorhabdus asymbiotica. FEMS Microbiology Letters, 309 (2), pp. 136-143.
Jones, R. T., Sanchez-Contreras, M., Vlisidou, I., Amos, M. R., Yang, G., Munoz-Berbel, X., Upadhyay, A., Potter, U. J., Joyce, S. A., Ciche, T. A., Jenkins, A. T. A., Bagby, S., ffrench-Constant, R. H. and Waterfield, N. R., 2010. Photorhabdus adhesion modification protein (Pam) binds extracellular polysaccharide and alters bacterial attachment. BMC Microbiology, 10, 141.
Waterfield, N., 2010. Host–pathogen interactions: Proline gives insect pathogens the green light. Current Biology, 20 (1), R13-R15.
Poulter, N., Munoz-Berbel, X., Johnson, A. L., Dowling, A. J., Waterfield, N. and Jenkins, A. T. A., 2009. An organo-silver compound that shows antimicrobial activity against Pseudomonas aeruginosa as a monomer and plasma deposited film. Chemical Communications, 2009 (47), pp. 7312-7314.
Vlisidou, I., Dowling, A. J., Evans, I. R., Waterfield, N., ffrench-Constant, R. H. and Wood, W., 2009. Drosophila embryos as model systems for monitoring bacterial infection in real time. PLoS Pathogens, 5 (7), e1000518.
Wilkinson, P., Waterfield, N. R., Crossman, L., Corton, C., Sanchez-Contreras, M., Vlisidou, I., Barron, A., Bignell, A., Clark, L., Ormond, D., Mayho, M., Bason, N., Smith, F., Simmonds, M., Churcher, C., Harris, D., Thompson, N. R., Quail, M., Parkhill, J. and ffrench-Constant, R. H., 2009. Comparative genomics of the emerging human pathogen Photorhabdus asymbiotica with the insect pathogen Photorhabdus luminescens. BMC Genomics, 10, pp. 302-324.
Eleftherianos, I., Waterfield, N. R., Bone, P., Boundy, S., Ffrench-Constant, R. H. and Reynolds, S. E., 2009. A single locus from the entomopathogenic bacterium Photorhabdus luminescens inhibits activated Manduca sexta phenoloxidase. FEMS Microbiology Letters, 293 (2), pp. 170-176.
Plichta, K. L., Joyce, S. A., Clarke, D., Waterfield, N. and Stock, S. P., 2009. Heterorhabditis gerrardi n. sp (Nematoda: Heterorhabditidae): the hidden host of Photorhabdus asymbiotica (Enterobacteriaceae: gamma-Proteobacteria). Journal of Helminthology, 83 (4), pp. 309-320.
Waterfield, N. R., Ciche, T. and Clarke, D., 2009. Photorhabdus and a Host of Hosts. Annual Review of Microbiology, 63, pp. 557-574.
Ahantarig, A., Chantawat, N., Waterfield, N. R., Ffrench-Constant, R. and Kittayapong, P., 2009. PirAB Toxin from Photorhabdus asymbiotica as a Larvicide against Dengue Vectors. Applied and Environmental Microbiology, 75 (13), pp. 4627-4629.
Waterfield, N. R., Sanchez-Contreras, M., Eleftherianos, I., Dowling, A., Yang, G., Wilkinson, P., Parkhill, J., Thomson, N., Reynolds, S. E., Bode, H., Dorus, S. and ffrench-Constant, R., 2008. Rapid Virulence Annotation (RVA): identification of virulence factors using a bacterial genome library and multiple invertebrate hosts. Proceedings of the National Academy of Sciences of the United States of America, 105 (41), pp. 15967-15972.
Hares, M. C., Hinchliffe, S. J., Strong, P. C. R., Eleftherianos, I., Dowling, A. J., Ffrench-Constant, R. H. and Waterfield, N., 2008. The Yersinia pseudotuberculosis and Yersinia pestis toxin complex is active against cultured mammalian cells. Microbiology, 154, pp. 3503-3517.
