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Department of Biochemistry


Regulation of Virulence and Biofilm Formation by Pathogenic Bacteria

Work in the lab is focused on understanding how bacterial populations sense and respond to (i) one another and (ii) specific environmental challenges, and how they modulate their behaviour accordingly. In particular, we focus on how these factors affect virulence in two gram-negative model organisms; the opportunistic human pathogen, Pseudomonas aeruginosa, and the economically-important plant pathogen, Erwinia (now renamed Pectobacterium) atrosepticum. A special area of interest is in defining how changes in lifestyle (planktonic versus biofilm) influence cell-cell signaling and virulence factor production. Our work combines state-of-the-art proteomic, transcriptomic and metabolomic analyses with conventional molecular microbiological and biochemical approaches.

We work on clinical and environmental samples, as well as type (genome sequence) strains and collaborate closely with groups in the Chemistry Department to design and test novel low molecular weight blockers of specific biochemical and signaling pathways.

Current projects include regulation of type III secretion in biofilms (1, 3); structure-function analysis of the Pseudomonas quinolone signal (PQS) (4,5); function and regulation of genes associated with the “core” biofilm transcriptome in P. aeruginosa; the role of ppGpp in controlling virulence factor production (2, 8); the structure, function and regulation of a novel biofilm-specific metzincin protease (6).

More recently, we have also developed an interest in using next-generation DNA sequencing platforms to analyse the “global” genomic changes associated with chronic bacterial infections (7, 10).

Lab members: Catherine Fan, Audrey Crousilles, Eve Maunders, Yssy Baker (Honorary resident Chemist, but who really belongs to Dave Spring), Ana Duarte (visiting Scientist) and James Wagstaff.

Very recently departed (but missed) members..... Sanaya Patell, Ian Passmore, Peter Davenport, James Hodgkinson, Jade Chung, Steve Bowden, Udi "Edward" Gabbai, Elina and Ahir.

Selected publications:

1      Type III secretion system expression in oxygen-limited Pseudomonas aeruginosa cultures is     stimulated by isocitrate lyase activity. Jade CS Chung, Olena Rzhepishevska, Madeleine Ramstedt, , Martin Welch. Open Biology 3(1):120131. doi: 10.1098/rsob.120131 (2013).

2      Virulence in Pectobacterium atrosepticum is regulated by a coincidence circuit involving quorum sensing and the stress alarmone, (p)ppGpp. Steven D. Bowden, Alison Eyres, Jade C.S. Chung, Rita E. Monson, Arthur Thompson, George P.C. Salmond, David R. Spring and Martin Welch. Molecular Microbiology 90 : 457-471 (2013).

3      Mikkelsen H, Bond N, Skindersoe ME, Givskov M, Lilley KS and Welch M. “Biofilms and Type III secretion are not mutually exclusive in Pseudomonas aeruginosa”. 155: 687-698. Microbiology (2008).

4      James Hodgkinson, Steven D. Bowden, Warren R. J. D. Galloway, David R. Spring and Martin Welch. Structure-activity analysis of the Pseudomonas quinolone signal molecule. J. Bacteriol. 192 :3833-3837 (2010).

5      Ligand binding kinetics of the quorum sensing regulator PqsR. Martin Welch, James Hodgkinson, Jeremy Gross, David Spring, Thomas Sams. Biochemistry 52 : 4433-4438 (2013).

6      Ian J Passmore, Kahoko Nishikawa, Kathryn S Lilley, Steven D Bowden, Jade CS Chung and Martin Welch.Mep72: A metzincin protease that is preferentially secreted by biofilms of Pseudomonas aeruginosa. J. Bacteriol. In Press (2014). 

7      Genomic variation among contemporary Pseudomonas aeruginosa isolates from chronically-infected cystic fibrosis patients. Jade C. S. Chung, Jennifer Becq, Louise Fraser, Ole Schulz-Trieglaff, Nicholas J. Bond, Juliet Foweraker, Kenneth D. Bruce, Geoffrey P. Smith and Martin Welch. J. Bacteriol. 194:4857-4866 (2012).

8      Wang J-H, Gardiol. N., Burr, T., Salmond GPC, and Welch M “RelA-dependent (p)ppGpp production controls exoenzyme synthesis in Erwinia carotovora subsp. atroseptica.” J. Bacteriol 189: 7643-7652 (2007).

9      Surface swarming motility by Pectobacterium atrosepticumis a latent phenotype that requires O antigen and is regulated by quorum sensing.  Steven D. Bowden, Nicola Hale, Jade C.S. Chung, James T. Hodgkinson, David R. Spring and Martin Welch. Microbiology 159 : 2375-2385 (2013).

10     Universal soldier : Pseudomonas aeruginosa, an opportunistic generalist. Frontiers in Biology (In Press 2013). Jeremy Gross, Ian J. Passmore, Jade CS Chung, Olena Rzhepishevska Madeleine Ramstedt, Martin Welch.