Mark AchtmanTeresa BarbosaDavid ClarkeAvril CoghlanJ. Kevin CollinsAlan DobsonMax DowGerald F. FitzgeraldCormac GahanColin HillJohn MorganJohn P. MorrisseyFergal O' GaraNiall O' LearyPaul O' TooleMichael B. PrenticeMartina ScallanCarmel ShortissDouwe van Sinderen

Biography

Academic Career

1969-1972: Natural Sciences Tripos, University of Cambridge

1972-1975: PhD Biochemistry, University of  Cambridge 

1975-1978: Research Fellow, University of Leeds

1979-1983: Research Associate/College Assistant Professor, New Mexico State University, U.S.A.

1984: EMBO Fellow, University of Groningen, The Netherlands 

1985-1987: Higher Scientific Officer, Department of Cell Biology, John Innes Institute, Norwich, U.K.

1988- 2002: Research Scientist, The Sainsbury Laboratory, John Innes Centre, Norwich, U.K.

2002-2003: E.T.S. Walton Visiting Fellow, (SFI), University College Cork, Ireland

2004-present: SFI Principal Investigator, University College Cork, Ireland

Teaching areas

• Molecular Microbiology
• Environmental Microbiology and Biotechnology

Research interests and expertise

• Cyclic di-GMP signalling in the regulation of virulence of human and plant pathogens
• Lipopolysaccharides and the induction of defence responses in plants
• Induced systemic resistance and biocontrol of plant diseases by beneficial bacteria

Research

Research Overview

Cyclic di-GMP signalling in the regulation of virulence of human and plant pathogens

Virulence factor production in bacterial pathogens of both humans and plants is tightly regulated and can occur in response to particular environmental cues. We are particularly interested in signal transduction systems that link the sensing of environmental cues to changes in bacterial behaviour through modulation of the levels of the second messenger cyclic di-GMP. These regulatory systems are widely conserved in bacterial species, including pathogens of humans, animals and plants, although their roles are poorly understood. A greater understanding of the molecular bases of these signalling processes could underpin new strategies to combat bacterial disease.

We have previously shown that the HD-GYP domain regulator RpfG of the plant pathogen Xanthomonas campestris is part of a signal transduction system that controls virulence and biofilm dispersal in response to the diffusible signal factor DSF. More recently we have shown that the HD-GYP domain of RpfG is a phosphodiesterase acting to degrade the intracellular second messenger cyclic-di-GMP. HD-GYP domain proteins act in conjunction with proteins containing two other domains, (GGDEF and EAL) to modulate the level of cyclic-di-GMP, in response to environmental cues. The GGDEF domain is a diguanylate cyclase involved in synthesis of the nucleotide whereas the EAL domain is a cyclic di-GMP phosphodiesterase. We are currently examining (i) the regulatory role of the HD-GYP domain proteins of the human pathogen Pseudomonas aeruginosa, using both transcriptome and proteome analyses (ii) the regulatory interplay and physical interaction between different cyclic di-GMP signalling proteins with HD-GYP and GGDEF domain (iii) the mechanisms by which cyclic di-GMP exerts its broad influence on diverse bacterial functions.

Lipopolysaccharides and the induction of defence responses in plants

We are using the interaction between the Gram-negative bacterium Xanthomonas campestris and host plants such as Arabidopsis thaliana as a model system to investigate molecular mechanisms underlying plant disease and disease resistance. In particular we are investigating the role of lipopolysaccharides (LPS) of Xanthomonas campestris in triggering innate immune defences in plants. Although the role of LPS in triggering innate and adaptive immunity in animals is well established, effects of LPS in plants remain relatively poorly understood and plant receptors for LPS have not yet been identified. We have identified that lipid A, core oligosaccharide and O-antigen substructures within the LPS of Xanthomonas campestris can all trigger defence-related gene expression in Arabidopsis plants. Currently we are trying to identify elements in the signalling pathways that lead to defence-related gene expression, including putative receptors for LPS.

Induced systemic resistance and biocontrol of plant diseases by beneficial bacteria

Current methods of controlling plant disease in agriculture vary from crop rotation to the application of chemicals. More recently the use of bacteria as biocontrol agents has attracted considerable interest as these potentially afford a more sustainable method of disease control. One such organism is Pseudomonas fluorescens F113 which produces the secondary metabolite 2, 4-diacetylphloroglucinol (DAPG) that has been shown to be antifungal, antibacterial and highly inhibitory against the potato cyst nematode Globodera rostochiensis. As well as a having a direct action against pathogens, DAPG has been shown to induce systemic resistance in a number of plants including Arabidopsis, tomato and barley. DAPG has also been shown to alter plant root exudation, an important signalling mechanism between plants and both beneficial and pathogenic rhizospheric microorganisms. We are interested in understanding how DAPG exerts these diverse effects in plants. To this end we are examining the influence of application to barley roots of P. fluorescens F113 and an isogenic DAPG-minus strain on the plant transcriptome. We expect that the findings will contribute to an enhanced understanding of the complex of interactions that occur within the rhizosphere, which has the potential to lead to major developments in sustainable agricultural practices.

Selected Recent Publications

Cyclic di GMP signalling

The c-AMP Receptor-Like Protein CLP is a Novel c-di-GMP Receptor Linking Cell-Cell Signaling to Virulence Gene Expression in Xanthomonas campestris  K.-H. Chin, Y.-C. Lee, Z.-L. Tu, C.-H. Chen, Y.-H. Tseng, J.-M. Yang , R. P. Ryan , Y. McCarthy , J. M. Dow, A. H.-J. Wang and S.-H. Chou (2010) J. Mol. Biol. 396: 646-662.

Cell-cell signal dependent dynamic interactions between HD-GYP and GGDEF domain proteins mediate virulence in Xanthomonas campestris. R. P. Ryan, Y. McCarthy, M. Andrade C. S. Farah, J.P. Armitage and J. M. Dow (2010) Proc. Natl. Acad. Sci. USA 107: 5989-5994

The HD-GYP domain and cyclic di-GMP signaling R. P. Ryan, Y. McCarthy and J. M. Dow. (2009) in The second messenger cyclic di-GMP Alan J. Wolfe and Karen L. Visick (eds) ASM Press

HD-GYP domain proteins regulate biofilm formation and virulence in Pseudomonas aeruginosa. R. P. Ryan, J. Lucey, K. O’Donovan, Y. McCarthy, L. Yang, T. Tolker-Nielsen and J. M. Dow. (2009) Environ. Microbiol. 11: 1126-1136.

The role of PilZ domain proteins in the virulence of Xanthomonas campestris pathovar campestris Y. McCarthy, R. P. Ryan, K. O’Donovan, Y.-Q. He, B.-L. Jiang, J.-X. Feng, J.-L. Tang and J. M. Dow. (2008) Mol. Plant Pathol. 9: 819-824.

Diversification of the function of cell-to-cell signaling in regulation of virulence within plant pathogenic xanthomonads, M. Dow (2008). Science Signaling, 1, pe23

Cyclic di-GMP signalling and the regulation of virulence in bacterial plant pathogens. J. M. Dow, Y. Fouhy, B. Fernandez Garcia and R. P. Ryan (2008) In Plant pathogenic bacteria: Genomics and Molecular Biology R. W. Jackson (ed) Horizon Scientific Press, Norwich UK.

Controlled synthesis of the DSF cell-cell signal is required for biofilm formation and virulence in Xanthomonas campestris. P. S. Torres, F. Malamud, L. A. Rigano, D.M. Russo., M. R. Marano., A. P. Castagnaro, A. Zorreguieta, K. Bouarab, J. M. Dow and A. A. Vojnov (2007) Environ Micro 9 : 2101-2109

DSF-dependent cell-cell signaling and virulence in the nosocomial pathogen Stenotrophomonas maltophilia Y. Fouhy, K. Scanlon, K. Schouest, C. Spillane, L. Crossman, M. B. Avison, R. P. Ryan and J. M. Dow (2007) J Bacteriol 189: 4964-4968

Cyclic di-GMP as an intracellular signal regulating bacterial biofilm formation J. M. Dow, Y. Fouhy, J. Lucey and R. P. Ryan (2007) In Bacterial biofilm formation and adaptation S.Kjelleberg and M.Givskov (eds) Horizon Scientific Press, Norwich UK

Cyclic di-GMP signalling in the virulence and environmental adaptation of Xanthomonas campestris R. P. Ryan, Y. Fouhy, J.F. Lucey, B.-L. Jiang, Y.-Q. He, J.X. Feng, J.-L. Tang and J. M. Dow (2007) Mol Microbiol 63: 429-442.

The HD-GYP domain, cyclic di-GMP signaling and bacterial virulence to plants. J. M. Dow, Y. Fouhy, J.F. Lucey and R. P. Ryan (2006) Mol Plant-Microbe Interact 19: 1378-1384.

Cell-cell signalling, cyclic di-GMP turnover and the regulation of virulence in Xanthomonas campestris. Y. Fouhy, J.F. Lucey, R. P. Ryan and J. M. Dow (2006) Res Microbiol. 10: 899-904.

Cyclic di-GMP signaling in bacteria: recent advances and new puzzles. R. P. Ryan, Y. Fouhy, J.F. Lucey and J. M. Dow (2006) J. Bacteriol. 188: 8327-8334.

Dual signaling functions of the hybrid sensor kinase RpfC of Xanthomonas campestris involve either phosphorelay or receiver domain-protein interaction Y.-W. He, J. M.Dow and L.-H. Zhang (2006) J Biol Chem 281: 33414-33421.

Cell-cell signaling in Xanthomonas campestris involves an HD-GYP domain protein that functions in cyclic di-GMP turnover. R. P. Ryan, Y. Fouhy, J.F. Lucey, L. C. Crossman, S. Spiro, Y.-W. He, L.-H. Zhang, S. Heeb, P. Williams and J. M. Dow (2006) Proc Natl Acad Sci USA 103: 6712-6717.

Genome scale analysis of DSF regulon in Xanthomonas campestris pv. campestris: identification of novel cell-cell communication-dependent genes and functions Y.-W. He, M. Xu, K. Lin, Y.-J. A. Ng, C.-M. Wen,.L.-H. Wang, Z.-D. Liu, H.-B. Zhang, Y.-H. Dong, J. M.Dow and L.-H. Zhang (2006) Mol Microbiol 59: 610-622.

Recent Publications on other aspects of host-microbe interactions

Glyco-conjugates as elicitors or suppressors of plant innate immunity
A. Silipo, G. Erbs, T. Shinya, J. M. Dow, M. Parrilli, R.Lanzetta, N. Shibuya, M.-A. Newman and A. Molinaro  (2010) Glycobiology 20: 406–419.

Lipopolysaccharides and plant innate immunity G. Erbs, A. Molinaro, J. M. Dow and M.-A. Newman (2010) in Subcellular Biochemistry Vol 53 Endotoxins: Structure, function and recognition Edited by P. J. Quinn and X. Wang Springer ISBN: 978-90-481-9077-5

Bacteria causing important diseases of citrus utilise distinct modes of pathogenesis to attack a common host A. A. Vojnov, A. M. do Amaral, J. M. Dow, A. P. Castagnaro and M. R. Marano Appl. Microbiol. Biotechnol. doi: 10.1007/s00253-010-2631-2 

Intraspecies signaling involving the diffusible signal factor BDSF influences virulence in Burkholderia cenocepacia R. P. Ryan, Y. McCarthy, S. A. Watt, K. Niehaus and J. M. Dow (2009). J. Bacteriol. 191: 5013-5019.

Versatility and adaptation of bacteria from the genus Stenotrophomonas. R. P. Ryan, S. Monchy, M. Cardinale, S. Taghavi, L. Crossman, M. B. Avison, G. Berg, D. van der Lelie and J. M. Dow. (2009) Nature Reviews in Microbiology 7: 514-525

The H-NS-like protein-encoding gene xrvA of Xanthomonas oryzae pv. oryzae regulates virulence in rice. J.-X. Feng, Z.-Z. Song, C.-J. Duan, S. Zhao, Y.-Q. Wu, C. Wang, J. M. Dow, and J.-L. Tang (2009) Microbiology 155: 3033-3044.

Microbial glycosylated components in plant disease. M. Dow, A. Molinaro, R.M. Cooper, M.-A. Newman (2009) In Microbial Glycobiology Structures, Relevance and Applications A. Mora, P. Brennan, O. Holst. M von Itszstein (eds) San Diego, CA, USA: Elsevier,. pp. 803-820 ISBN 978-0-12-374546-0

Acquisition and Evolution of Plant Pathogenesis–Associated Gene Clusters and Candidate Determinants of Tissue-Specificity in Xanthomonas. H. Lu, P. Patil, M.-A. Van Sluys, F. F. White, R. P. Ryan, J. M. Dow, P. Rabinowicz, S. L. Salzberg, J. E. Leach, R. Sonti, V. Brendel, and A. J. Bogdanove (2008) PloSONE 3: e3828

An antagonist of lipid A action in mammals has complex effects on lipid A induction of defence responses in the model plant Arabidopsis thaliana G. Erbs, T. Tandrup Jensen, A. Silipo, W. Grant, J. M. Dow, A. Molinaro, M. Parrilli, and M.-A. Newman (2008) Microbes Infection 10: 571-574

Diffusible signals and interspecies communication in bacteria R. P. Ryan and J. M. Dow (2008) Microbiology 154: 1845-1858.

Genome sequence and rapid evolution of the rice pathogen Xanthomonas oryzae pv. oryzae PXO99A. S.L. Salzberg, D.D. Sommer, M.C. Schatz, A.M. Phillippy, P.D. Rabinowicz, S. Tsuge, A. Furutani, H. Ochiai, A.L. Delcher, D. Kelley, R. Madupu, D. Puiu, D. Radune, M. Shumway, C. Trapnell, G. Aparna, G. Jha, A. Pandey, P.B. Patil, H. Ishihara, D.F. Meyer, B. Szurek, V. Verdier, R. Koebnik, J.M. Dow, R.P. Ryan, H. Hirata, S. Tsuyumu, S.W. Lee, P.C. Ronald, R.V. Sonti, M.-A. Van Sluys, J.E. Leach, F.F.White and A.J Bogdanove. (2008). BMC Genomics 9: 204.

The complete genome of the opportunistic pathogen Stenotrophomonas maltophilia reveals a tenacious organism heavily shielded by drug resistance determinants. L.C. Crossman, V. C. Gould, J. M. Dow, G. S. Vernikos, A. Okazaki, M. Sebaihia, D. Saunders, C. Arrowsmith, T. Carver, N. Peters, A. Lord, L. Murphy, K. Seeger, R. Squares, S. Rutter, M. A. Quail, D. Harris, M.-A. Rajandream, C. Churcher, J. Parkhill, S. D. Bentley, N. R. Thomson and M. B. Avison (2008) Genome Biology 9: R74

Interspecies signalling via the Stenotrophomonas maltophilia diffusible signal factor influences biofilm formation and polymyxin tolerance in Pseudomonas aeruginosa

R.P. Ryan, Y. Fouhy, B. Fernandez Garcia, S. A. Watt, K. Niehaus, L. Yang, T. Tolker-Nielsen and J. M. Dow (2008) Mol. Microbiol. 68:75-86.

The acylation and phosphorylation pattern of lipid A from Xanthomonas campestris strongly influence its ability to trigger the innate immune response in Arabidopsis A. Silipo, L. Sturiale, G. Erbs, D. Garozzo, T. Tandrup Jensen, R. Lanzetta, J. M. Dow, M. Parrilli, M.-A. Newman and A. Molinaro (2008) ChemBiochem 9: 896-904.

A putative RNA binding protein has a role in virulence in Ralstonia solanacearum GMI1000 A. Franks, G. L. Mark-Byrne, J. M. Dow, F. O’Gara (2008) Mol. Plant Pathol. 9: 67-72.A putative RNA binding protein has a role in virulence in Ralstonia solanacearum GMI1000 A. Franks, G. L. Mark-Byrne, J. M. Dow, F. O’Gara (2008) Mol. Plant Pathol.

Biofilm formation, epiphytic fitness and canker development in Xanthomonas axonopodis pv. citri. L. Rigano, F. Siciliano, R. Enrique, L. Sendín, P. Filippone, P. Torres, J. Qüesta, J.M. Dow, A. Castagnaro, A.A.Vojnov and M. R. Marano. (2007) Mol. Plant Microb. Int. 20: 1222-1230.

Bacterial Cyclic eta-(1, 2) Glucan Acts in Systemic Suppression of Plant Immune Responses L.A Rigano, C. Payette, G. Brouillard, M. R. Marano, L. Abramowicz, P. S. Torres, M. Yun, A. P. Castagnaro, M. El Oirdi, V. Dufour, F. Malamud, J. M. Dow, K. Bouarab and A. A. Vojnov. (2007) The Plant Cell 19: 2077-2089.

Sequence-based analysis of pQBR103; a representative of a unique, transfer-proficient mega plasmid resident in the microbial community of sugar beet
A Tett, A. J. Spiers, L. C. Crossman, D. Ager, L. Ciric, J. M. Dow, J. Fry, D. Harris, A. Lilley, J. Parkhill, M. A. Quail, P. B. Rainey, N. J. Saunders, K. Seeger, L. A. S. Snyder, R. Squares, C. Thomas, S. L. Turner, X.-X. Zhang, D. Field and M. J. Bailey (2007) The ISME J. 1: 331-340.

Priming, induction and modulation of plant defence responses by bacterial lipopolysaccharides. M.-A. Newman , J. M. Dow, A. Molinaro, and M. Parrilli (2007) J. Endotoxin Res. 13: 68-79.

Structure-dependent modulation of pathogen responses in plants by synthetic O-antigen polysaccharides. E. Bedini, C. De Castro, L. Mangoni, G. Erbs, J. M. Dow, M.-A. Newman, M. Parrilli and C. Unverzagt (2005) J. Am. Chem. Soc 127:2414 –2416.

Modulation of Quorum Sensing in Pseudomonas aeruginosa through alteration of membrane properties. C. Baysse, M. Cullinane, V. Dénervaud, E. Burrowes J. M.Dow, J.P. Morrissey, L.Tam, J.T. Trevors and F. O’Gara (2005) Microbiology 151: 2529-2542.

The elicitation of plant innate immunity by lipooligosaccharide of Xanthomonas campestris A. Silipo, A. Molinaro, L. Sturiale, J. M. Dow, G. Erbs, R. Lanzetta, M.-A. Newman, M. Parrilli (2005) J. Biol. Chem. 280: 33660-33668.

Transcriptome profiling of bacterial responses to root exudates identifies novel genes involved in microbe-plant interactions. G. L. Mark, J. M.Dow, P. D. Kiely, H. Higgins, J. Haynes, C. Baysse, A. Abbas, T. Foley, A. Franks, J. Morrissey and F. O’Gara (2005) Proc Natl Acad Sci USA 102: 17454-17459.

Research funding and grants

The work is funded by grants from the Science Foundation of Ireland, Department of Agriculture & Food, Enterprise Ireland, Human Frontiers Science Programme and EMBO

Research Group Members

SFI funded research:

Dr Robert Ryan

Ms Yvonne McCarthy

Ms Karen O’Donovan

Ms Aileen O’Connell

Mr Dong-Jie Tang

DAFF funded research:

Dr Ruth Nevin

Ms Jen McCarthy

International Research collaborators

Prof Ji-Liang Tang, The Key Laboratory for Subtropical Bioresources Conservation and Utilisation, Guangxi University, PRC

Prof Paul Williams, Director Institute of Infections, Immunity and Inflammation, University of Nottingham, UK.

Dr Matthew Avison, Department of Pathology and Microbiology, University of Bristol, UK

Dr Lisa Crossman Wellcome Trust Sanger Institute, Hinxton UK

Prof Adam Bogdanove, Department of Plant Pathology, Iowa State University, USA

Prof Chuck Farah, University of São Paulo, Brazil

Dr Adrian Vojnov, Fundacion Cassara, Buenos Aires, Argentina

Prof Karsten Niehaus, Department of Proteome and Metabolome Research, Bielefeld University, Germany,

Prof Tim Tolker-Nielsen, Centre for Biomedical Microbiology Technical University of Denmark, now at University of Copenhagen

Prof Judith Armitage Department of Biochemistry, University of Oxford, UK

Dr Martin Walsh, EMBL, Grenoble, France and Diamond UK.

Dr Mari-Anne Newman, University of Copenhagen.

Prof Antonio Molinaro, Università di Napoli Federico II, Italy.

Prof Shan-Ho Chou, Institute of Biochemistry, National Chung-Hsing University, Taichung, Taiwan, ROC.

Prof Yi-Hsiung Tseng, Institute of Microbiology, Immunology, and Molecular Medicine, Tzu Chi University, Hualien 970, Taiwan, ROC