1. Molecular microbiology and physiology of Campylobacter and Helicobacter
Research in my laboratory is mainly focussed on understanding the physiology of two important and related human pathogens - Campylobacter jejuni and Helicobacter pylori. The aim is to elucidate fundamental aspects of the metabolism of these bacteria that relate to stress responses and survival in the environment and to growth in the host.
Campylobacter jejuni
Campylobacters are common animal pathogens and C. jejuni is
now the most frequent cause of human food-borne gastroenterits in the western world. C. jejuni is a commensal of many species of birds, and colonisation of poultry is a particular problem. Our work is centered on understanding the following aspects of physiology of this bacterium (i) How does C. jejuni adapt to the low oxygen conditions found in the gut? We are investigating the nature and functions of the various respiratory chains, the response of C. jejuni to varying oxygen concentrations and its ability to resist oxidative stress. (ii) What are the metabolic pathways used by C. jejuniin vivo? We have found that amino-acid transport and catabolism is of major importance and we have several projects to characterise the various pathways involved.
Helicobacter pylori
Since its discovery in 1982, H. pylori has come to be recognised as perhaps the commonest bacterial infection in Man and is the causative agent of certain types of gastritis and virtually all duodenal and most gastric ulcers. Long-term infection with H. pylori is also a risk factor for gastric cancer. Despite its obvious importance as a pathogen, we still know surprisingly little about the fundamental biology of this fascinating bacterium which occupies a unique ecological niche. We are currently investigating two major areas; (i) the respiratory chain and the molecular basis for microaerophilic growth (ii), central metabolic pathways and the identification of novel enzymes as potential new targets for anti-microbial chemotherapy.
2. The ‘TRAP’ transporter family - A New Type of Bacterial Solute Transporter
A second area of interest has arisen out of our discovery of a completely new family of Tripartite, ATP-independent Periplasmic (‘TRAP’) bacterial solute transport systems, which rely on a periplasmic-binding protein for their operation but which appear to be energised by the proton-motive force rather than by ATP hydrolysis as in "conventional" periplasmic tranporters. We are investigating the structure, function and mechanism of these novel
systems, which appear to be widespread in many types of bacteria and archea, including pathogens, photosynthetic and denitrifying bacteria. This work is being carried out in collaboration with Dr Gavin H. Thomas, Department of Biology, University of York, UK.
Figure 1 - Campylobacter jejuni, causative agent of human food-borne gastroenteritis.
Figure 2 - Helicobacter pylori, the causative agent of
gastric and duodenal ulcers, and a risk factor for gastric cancer.
Selected Publications
Myers, J.D. and Kelly, D.J. (2005) A sulphite respiration system in the chemoheterotrophic human pathogen Campylobacter jejuni Microbiology 151, 233-242
Velayudhan, J., Jones, M., Barrow, P.A. and Kelly, D.J. (2004) L-serine catabolism via an oxygen labile L-serine dehydratase (SdaA)
is essential for colonisation of the avian gut by Campylobacter jejuni. Infection and Immunity, 72, 260-268.
Comtois, S., Gidley, M. and Kelly, D.J. (2003) The role of the thioredoxin system and the thiol-peroxidases Tpx and Bcp in mediating
resistance to oxidative and nitrosative stress in Helicobacter pylori. Microbiology. 149, 121-129.
Sellars, M.J., Hall, S.J. and Kelly, D.J. (2002) Growth of Campylobacter jejuni supported by respiration of fumarate, nitrate, nitrite, trimethylamine-N-oxide or dimethylsulfoxide requires oxygen. Journal of Bacteriology, 184, 4187-4196.
Waidner, B., Greiner, S., Odenbreit, S., Kavermann, H., Velayudhan, J., Stahler, F., Guhl, J., Bisse, E., van Vliet, A.H.M, Andrews, S., Kusters, J.G., Kelly, D.J., Haas, R., Kist, M. and Bereswill, S. (2002). Essential role of ferritin Pfr in Helicobacter pylori iron metabolism and gastric colonisation. Infection and Immunity 70, 3923-3929.
Velayudhan, J., and Kelly, D.J. (2002) Analysis of gluconeogenic
and anaplerotic enzymes in Campylobacter jejuni: An essential role for phosphoenolpyruvate carboxykinase. Microbiology 148, 685-694.
Kelly, D.J. (2001). The physiology and metabolism of Campylobacter
jejuni and Helicobacter pylori. Journal of Applied Microbiology 90, 16S-24S.
Kelly, D.J. and Thomas, G.H. (2001) The tripartite ATP-independent
periplasmic (TRAP) transporters of bacteria and archaea. FEMS Microbiology Reviews 25, 405-424.
Velayudhan, J., Hughes, N. J., McColm, A.A., Bagshaw, J., Clayton, C.L., Andrews, S.A. and Kelly, D.J. (2000) Iron acquisition and virulence in Helicobacter pylori: a major role for FeoB, a high-affinity ferrous iron transporter.. Molecular Microbiology 37, 274-286.
