Molecular Microbiology

Prof D J Kellyim-d-k-06.jpg

blank spaceCareer history

1999-present Professor of Microbial Physiology, University of Sheffield
1998-199 Reader in Microbiology, University of Sheffield
1996-1998 Senior Lecturer in Microbiology, University of Sheffield
1986-1996 Lecturer in Microbiology, University of Sheffield
1985-1986 SERC PDRA, University of Birmingham
1982-1985 Ph.D. University of Warwick

Research interests

1. Molecular microbiology, physiology and biochemistry of Campylobacter
Campylobacters are an important group of human pathogens and C. jejuni is the most frequent cause of human food-borne gastroenteritis in the western world with hundreds of thousands of cases occurring annually in the UK alone. C. jejuni is a commensal in many species of birds, and colonisation of poultry is a particular problem for contamination of the human food chain, as undercooked chicken is thought to be responsible for about 75% of human infections. Human campylobacteriosis is usually a self-limiting disease but in a significant number of cases serious auto-immune sequelae can result, such as Guillain-Barre syndrome and reactive arthritis.
If we are to control the entry of this bacterium into the food chain, it is essential that we understand the fundamental physiology of campylobacters and their relationship with their hosts, so that effective intervention measures may be put in place.
Our work is centered on understanding a variety of aspects of the molecular biology, physiology and biochemistry of this important bacterium. Some recent and current examples of projects include:

(i) How does C. jejuni conserve energy? We are investigating the nature and functions and mechanism of assembly of the various respiratory chains in the bacterium, which are far more complex than would be predicted for a small genome pathogen and some of which have novel features (e.g. see Guccione et al., 2010, Hitchcock et al., 2010, Thomas et al., 2011; Liu et al., 2013)

(ii) C. jejuni is an oxygen-sensitive microaerophilic bacterium. How does it protect itself against excess oxygen and adapt to the low oxygen conditions found in the gut? we are studying the response of C. jejuni to varying oxygen concentrations and its ability to resist oxidative stress. (e.g. see Atack and Kelly, 2008; Atack et al., 2008).

(iii) What are the transport and metabolic pathways used by C. jejuni in vivo? We have found that specific amino-acid transport and catabolism is of major importance and we have several projects to characterise various pathways of solute transport and metabolism. We are also interested in novel metabolic pathways in the cell, particularly those that may be important in growth and host colonization (e.g. see Guccione et al., 2008; Wright et al., 2009; Smart et al., 2009; Howlett et al., 2012).

(iv) How does C. jejuni interface with its hosts? We have identified proteins involved in the biogenesis and function of the outer membrane and we study how these proteins aid survival in and defend the bacteria against the host. (e.g. see Kale et al., 2011)

Figure 1:


2. Exploiting phototrophic bacteria and their enzymes to produce energy, biomass and useful products from lignocellulosic wastes
The phototrophic purple bacterium Rhodopseudomonas palustris is one of the most versatile bacteria known, with the ability to grow in a wide range of environments by respiration, photosynthesis and fermentation, under aerobic and anaerobic conditions with a large range of carbon sources from carbon dioxide to complex organic compounds, including lignin breakdown products. It also expresses three distinct nitrogenases, which catalyse the photoproduction of hydrogen. In this project we are investigating the potential of this bacterium to contribute to renewable energy production from lignin, by dissecting the transport and metabolic pathways for lignin monomer breakdown, using a combination of biochemical and genetic approaches (e.g. see Salmon et al., 2013). We are also interested in exploiting the wide range of enzymes for aromatic compound metabolism encoded in the genome for useful biotransformations.


Figure 2: Cells of Rhodopseudomonas palustris. Credit: F. Harrison. rhop8/rhop8.home.htm

Credit: F. Harrison. ( )


Fig 3: The 1.9Å resolution crystal structure of the periplasmic binding-protein CouP (RPA1789) from R. palustris with bound ferulate, an aromatic compound derived from lignin. (A) Representation of the overall fold with ferulate positioned in the binding cleft. Alpha helices are represented by red cylinders, loops by blue strands and beta-sheets by yellow arrows. (B) Ligplot representation of the interactions of ferulate with CouP (RPA1789). The key interactions are the H-bonds formed by His309 and Gln305 to the 4-OH group on the aromatic ring and also the H-bonds formed by Arg197/Thr102/Ser222 to the oxygen atoms of the carboxyl group of the ligand side-chain. See Salmon et al. (2013) for further details.

 3. Bacterial solute transport systems
An area of long-standing interest that overlaps with both of the topics described above is how bacteria get solutes into their cells. This 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 (e.g. see Salmon et al., 2013). Some of this work is being carried out in collaboration with Dr Gavin H. Thomas, Department of Biology, University of York, UK (e.g. see Mulligan et al., 2009; Mulligan et al., 2012) and also protein structure determinations with Dr John Rafferty at Sheffield.

Joining the lab.

I welcome applications from independently funded prospective international Ph.D students in any of the above areas to join the lab. Funded Ph.D studentships for UK and EU students are sometimes available. Please contact me in the first instance by e-mail:
Similarly, prospective postdocs and independently funded research fellows are welcome to contact me by e-mail.

 Selected publications from the Kelly lab:

LIU, Y-W., DENKMANN, K., KOSCIOV, N., DAHL, C. AND KELLY, D.J. (2013). Tetrathionate stimulated growth of Campylobacter jejuni identifies a new type of bi-functional tetrathionate reductase (TsdA) that is widely distributed in bacteria. Molecular Microbiology 88, 173-188.

SALMON R.C, CLIFF, M.J., RAFFERTY, J.B. AND KELLY DJ (2013) The CouPSTU and TarPQM Transporters in Rhodopseudomonas palustris: Redundant, Promiscuous Uptake Systems for Lignin-Derived Aromatic Substrates. PLoS ONE 8(3): e59844.

HOWLETT, R.M., HUGHES, B.M., HITCHCOCK, A. AND KELLY, D.J. (2012) Hydrogenase activity in the food-borne pathogen Campylobacter jejuni depends upon a novel ABC-type nickel transporter (NikZYXWV) and is SlyD independent. Microbiology. 158, 1645-1655.

MULLIGAN, C., LEECH, A.P., KELLY, D.J. AND THOMAS, GH. (2012). The membrane proteins SiaQ and SiaM form an essential stoichiometric complex in the sialic acid TRAP transporter SiaPQM (VC1777-1779) from Vibrio cholerae. Journal of Biological Chemistry 287, 3598-3608

KALE, A., PHANSOPA, C., SUWANNACHART, C., CRAVEN, C.J., RAFFERTY, J. AND KELLY, D.J. (2011) The virulence factor PEB4 and the periplasmic protein Cj1289 are two structurally related SurA-like chaperones in the human pathogen Campylobacter jejuni. Journal of Biological Chemistry. 286, 21254-21265.

THOMAS M.T., SHEPHERD M., POOLE R.K., VAN VLIET A.H., KELLY D.J., AND PEARSON B.M. (2011). Two respiratory enzyme systems in Campylobacter jejuni NCTC11168 contribute to growth on L-lactate. Environmental Microbiology 13, 48-61.

HITCHCOCK A., HALL S.J., MYERS J.D., MULHOLLAND F., JONES M.A. AND KELLY D.J. (2010) Roles of the twin-arginine translocase in the biogenesis of the electron transport chains of Campylobacter jejuni. Microbiology 156, 2994-3010.

GUCCIONE, E., HITCHCOCK, A., HALL, S.J., MULHOLLAND, F., SHEARER, N., VAN VLIET, A.H.M. AND KELLY, D.J. (2010) Reduction of fumarate, mesaconate and crotonate by Mfr, a novel oxygen-regulated periplasmic reductase in Campylobacter jejuni. Environmental Microbiology 12, 576-591.

SMART, J.P., CLIFF, M. AND KELLY, D.J. (2009) A role for tungsten in the biology of Campylobacter jejuni: tungstate stimulates formate dehydrogenase activity and is transported by an ultra-high affinity ABC system distinct from the molybdate transporter. Molecular Microbiology 74, 742-757.

MULLIGAN, C., GEERTSMA, E.R., SEVERI, E., KELLY, D.J., POOLMAN, B. AND THOMAS, G.H. (2009) The substrate-binding protein imposes directionality on an electrochemical sodium gradient-driven TRAP transporter. Proc. Natl. Acad. Sci. USA 106, 1778-1783.

WRIGHT, J.A., A. J. GRANT, D. HURD, M. HARRISON, E. J. GUCCIONE, D. J. KELLY AND D. J. MASKELL (2009). Metabolite and transcriptome analysis of Campylobacter jejuni in vitro growth reveals a stationary-phase physiological switch. Microbiology 155, 80-94.

HALL, S.J., HITCHCOCK, A., BUTLER, C.S. AND KELLY, D. J. (2008). A multicopper oxidase (Cj1516) and a CopA homologue (Cj1161) are major components of the copper homeostasis system of Campylobacter jejuni. Journal of Bacteriology, 190, 8075-8085.

ATACK, J.M. AND KELLY, D.J. (2008) Contribution of the stereospecific methionine sulphoxide reductases MsrA and MsrB to oxidative and nitrosative stress resistance in the food-borne pathogen Campylobacter jejuni. Microbiology. 154, 2219 – 2230

ATACK, J.M. HARVEY, P. JONES, M.A. AND KELLY, D.J. (2008) The Campylobacter jejuni thiol peroxidases Tpx and Bcp both contribute to aerotolerance and peroxide-mediated stress resistance but have distinct substrate specificities. Journal of Bacteriology. 190, 5279-5290

GUCCIONE, E.J., LEON-KEMPIS, M.D.R., PEARSON, B.M., HITCHIN, E., MULHOLLAND, F., VAN DIEMEN, P., STEVENS, M.P. AND KELLY, D.J. (2008) Amino-acid dependent growth of Campylobacter jejuni: Key roles for aspartase (AspA) under microaerobic and oxygen-limited conditions and identification of AspB (Cj0762), essential for growth on glutamate. Molecular Microbiology 69, 77-93.