Jacob Malone

Project Leader

Molecular Microbiology

Contact details

jacob.malone@jic.ac.uk

Research interests

My research addresses the molecular mechanisms underlying bacterial signal transduction during responses to the environment. To achieve this I employ a range of processes including genetics, cell and molecular microbiology and biochemistry. After six years in Switzerland, where I studied chronic bacterial infections in Cystic Fibrosis patients, I have recently started a new research group in the JIC studying the control of rhizosphere colonisation by the widespread Gram-negative bacterium Pseudomonas fluorescens.

Biocontrol agents; soil microorganisms that promote plant growth and/or suppress pathogens represent an attractive potential alternative to existing chemical pesticides. The commensal soil bacterium Pseudomonas fluorescens is a prominent biocontrol species that forms beneficial relationships with plants and suppresses fungal growth. The effectiveness of biocontrol is directly related to the effectiveness of bacterial rhizosphere colonisation. However, despite much research into biocontrol by P. fluorescens, the internal signalling systems within the bacteria that control root colonisation are only poorly understood. Recent work from our laboratory and others has identified an important role for the ubiquitous bacterial second messenger cyclic-di-GMP in the control of P. fluorescens root colonisation. Cyclic-di-GMP is found in almost every bacterial species on Earth, and is a critical component of the microbial decision-making machinery that controls when, where and how bacteria initiate biofilm formation, progress through the cell cycle, produce and secrete secondary metabolites or regulate motility and virulence factors.

In my previous laboratory, we used in-vitro expression technology (IVET) to identify a range of P. fluorescens genes that are specifically up-regulated in the rhizosphere. These include potential cdG targets such as the wss exopolysaccharide synthase operon, as well as several cdG-related operons. We have since shown that these rhizosphere up-regulated cdG systems control important aspects of bacterial behaviour, including attachment to plant roots and swarming motility. At least one system appears to be crucial for the effective colonisation of the wheat rhizosphere. My group is currently working to functionally characterise these cdG systems, with the overall aim of constructing an integrated molecular model for cdG signalling during the process of P. fluorescens rhizosphere colonisation.

Deletion of key cyclic-di-GMP genes results in a range of different motility defects in Pseudomonas fluorescens.

Selected Publications

The YfiBNR signal transduction mechanism reveals novel targets for the evolution of persistent Pseudomonas aeruginosa in cystic fibrosis airways J. G. Malone, T. Jaeger, P. Manfredi, A. Dötsch, A. Blanka, R. Bos, G. R. Cornelis, S. Häussler and U. Jenal, PLoS Pathogens (2012) manuscript accepted

YfiBNR mediates cyclic-di-GMP dependent small colony variant formation and persistence in Pseudomonas aeruginosa J. G. Malone, T. Jaeger, C. Spangler, D. Ritz, A. Spang, C. Arrieumerlou, V. Kaever, R. Landmann, and U. Jenal, PLoS Pathogens (2010), 6, e1000804

Genomic and genetic analyses of diversity and plant interactions of Pseudomonas fluorescens M. W. Silby, A. M. Cerdeño-Tárraga, G. S. Vernikos, S. R. Giddens, R. W. Jackson, G. M. Preston, X. X. Zhang, C. D. Moon, S. M. Gehrig, S. A. C. Godfrey, C. G. Knight, J. G. Malone, Z. Robinson, A. J. Spiers, S. Harris, G. L. Challis, A. M. Yaxley, D. Harris, K. Seeger, L. Murphy, S. Rutter, R. Squares, M. A. Quail, E. Saunders, K. Mavromatis, T. S. Brettin, S. D. Bentley, J. Hothersall, E. Stephens, C. M. Thomas, J. Parkhill, S. B. Levy, P. B. Rainey, and N. R. Thomson, Genome Biology (2009), 10, R51

Systematic mutagenesis of wspR; analysis of the structure-function relationship of a GGDEF response regulator J. G. Malone, R. Williams, M. Christen, U. Jenal, A. J. Spiers, and P. B. Rainey, Microbiology (2007), 153, pp 980-94

Mechanisms of cyclic-di-GMP signaling in bacteria U. Jenal and J. Malone, Annu Rev Genet (2006), 40, pp 385-407

Adaptive divergence in experimental populations of Pseudomonas fluorescens. II. The role of the GGDEF regulator WspR in evolution and development of the wrinkly spreader phenotype P.J. Goymer, S.G. Kahn, J. G. Malone, S. M. Gehrig, A. J. Spiers, and P. B. Rainey, Genetics (2006), 173, pp 515-26

Lab Members