Prof Dave Kelly
Professor of Microbiology
Tel: 0114 222 4414
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.
(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)
Microbiology, bacterial physiology, Campylobacter, Rhodopseudomonas, solute transport, metabolomics, proteomics
Research In Depth
Exploiting phototrophic bacteria and their enzymes to produce energy, biomass and useful products from lignocellulosic waste
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 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.
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.
MBB364 Microbiology Data Handling (Module Coordinator)
Honours and Distinctions
2010 - 2015: Senior Editor for Microbiology
2012 - 2015: External Examiner for the MRes in Post-genomic Biology at The University of York
2015: Keynote speaker, International Conference on Campylobacter, Helicobacter and Related Organisms (CHRO), Rotorua, New Zealand
- Yahara K, Méric G, Taylor AJ, de Vries SP, Murray S, Pascoe B, Mageiros L, Torralbo A, Vidal A, Ridley A, Komukai S, Wimalarathna H, Cody AJ, Colles FM, McCarthy N, Harris D, Bray JE, Jolley KA, Maiden MC, Bentley SD, Parkhill J, Bayliss CD, Grant A, Maskell D, Didelot X, Kelly DJ & Sheppard SK (2017) Genome-wide association of functional traits linked with Campylobacter jejuni survival from farm to fork. Environmental Microbiology, 19(1), 361-380. View this article in WRRO
- Al-Haideri H, White MA & Kelly DJ (2016) Major contribution of the type II beta carbonic anhydrase CanB (Cj0237) to the capnophilic growth phenotype of Campylobacter jejuni. Environmental Microbiology, 18(2), 721-735. View this article in WRRO
- Chintoan-Uta C, Cassady-Cain RL, Al-Haideri H, Watson E, Kelly DJ, Smith DGE, Sparks NHC, Kaiser P & Stevens MP (2015) Superoxide dismutase SodB is a protective antigen against Campylobacter jejuni colonisation in chickens. Vaccine, 33(46), 6206-6211.
- Liu Y-W & Kelly DJ (2015) Cytochrome c biogenesis in C ampylobacter jejuni requires cytochrome c (CccA; Cj1153) to maintain apocytochrome cysteine thiols in a reduced state for haem attachment. Molecular Microbiology, 96(6), 1298-1317.
- van der Stel A-X, van Mourik A, Heijmen-van Dijk L, Parker CT, Kelly DJ, van de Lest CHA, van Putten JPM & Wösten MMSM (2015) The C ampylobacter jejuni RacRS system regulates fumarate utilization in a low oxygen environment. Environmental Microbiology, 17(4), 1049-1064.
- Liu Y-W, Hitchcock A, Salmon RC & Kelly DJ (2014) It takes two to tango: two TatA paralogues and two redox enzyme-specific chaperones are involved in the localization of twin-arginine translocase substrates in Campylobacter jejuni.. Microbiology, 160(Pt 9), 2053-2066. View this article in WRRO
- Kendall JJ, Barrero-Tobon AM, Hendrixson DR & Kelly DJ (2014) Hemerythrins in the microaerophilic bacterium Campylobacter jejuni help protect key iron-sulphur cluster enzymes from oxidative damage.. Environ Microbiol, 16(4), 1105-1121. View this article in WRRO
- Bowden SD, Hopper-Chidlaw AC, Rice CJ, Ramachandran VK, Kelly DJ & Thompson A (2014) Nutritional and metabolic requirements for the infection of HeLa cells by Salmonella enterica serovar Typhimurium.. PLoS One, 9(5), e96266. View this article in WRRO
- Howlett RM, Davey MP, Paul Quick W & Kelly DJ (2014) Metabolomic analysis of the food-borne pathogen Campylobacter jejuni: application of direct injection mass spectrometry for mutant characterisation. Metabolomics, 1-10. View this article in WRRO
- Rasmussen JJ, Vegge CS, Frøkiær H, Howlett RM, Krogfelt KA, Kelly DJ & Ingmer H (2013) Campylobacter jejuni carbon starvation protein A (CstA) is involved in peptide utilization, motility and agglutination, and has a role in stimulation of dendritic cells. Journal of Medical Microbiology, 62(PART8), 1135-1143.
- Sheppard SK, Didelot X, Meric G, Torralbo A, Jolley KA, Kelly DJ, Bentley SD, Maiden MCJ, Parkhill J & Falush D (2013) Genome-wide association study identifies vitamin B5 biosynthesis as a host specificity factor in Campylobacter. Proceedings of the National Academy of Sciences of the United States of America, 110(29), 11923-11927.
- Liu Y-W, Denkmann K, Kosciow K, Dahl C & Kelly DJ (2013) Tetrathionate stimulated growth of Campylobacter jejuni identifies a new type of bi-functional tetrathionate reductase (TsdA) that is widely distributed in bacteria.. Mol Microbiol, 88(1), 173-188.
- Salmon RC, Cliff MJ, Rafferty JB & 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. View this article in WRRO
- Avila-Ramirez C, Tinajero-Trejo M, Davidge KS, Monk CE, Kelly DJ & Poole RK (2013) Do globins in microaerophilic Campylobacter jejuni confer nitrosative stress tolerance under oxygen limitation?. Antioxid Redox Signal, 18(4), 424-431.
- Howlett RM, Hughes BM, Hitchcock A & Kelly DJ (2012) Hydrogenase activity in the foodborne pathogen Campylobacter jejuni depends upon a novel ABC-type nickel transporter (NikZYXWV) and is SlyD-independent.. Microbiology, 158(Pt 6), 1645-1655.
- Sheppard SK, Jolley KA, Cody A, Colles FM, Mccarthy ND, Maiden MCJ, Pascoe B, Meric G, Didelot X, Darling AE, Kelly DJ, Strachan NJC, Ogden ID, Forbes K, French NP, Carter P, Miller WG, Owen R, Litrup E, Egholm M, Affourtit JP, Bentley SD, Parkhill J & Falush D (2012) Progressive genome-wide introgression in agricultural Campylobacter coli. Molecular Ecology.
- Mulligan C, Leech AP, Kelly DJ & Thomas GH (2012) The membrane proteins SiaQ and SiaM form an essential stoichiometric complex in the sialic acid tripartite ATP-independent periplasmic (TRAP) transporter SiaPQM (VC1777-1779) from Vibrio cholerae. Journal of Biological Chemistry, 287(5), 3598-3608.
- Kale A, Phansopa C, Suwannachart C, Craven CJ, Rafferty JB & Kelly DJ (2011) The virulence factor PEB4 (Cj0596) and the periplasmic protein Cj1289 are two structurally related SurA-like chaperones in the human pathogen Campylobacter jejuni.. J Biol Chem, 286(24), 21254-21265.
- Thomas MT, Shepherd M, Poole RK, van Vliet AHM, Kelly DJ & Pearson BM (2011) Two respiratory enzyme systems in Campylobacter jejuni NCTC 11168 contribute to growth on L-lactate.. Environ Microbiol, 13(1), 48-61.
- Hitchcock A, Hall SJ, Myers JD, Mulholland F, Jones MA & Kelly DJ (2010) Roles of the twin-arginine translocase and associated chaperones in the biogenesis of the electron transport chains of the human pathogen Campylobacter jejuni.. Microbiology, 156(Pt 10), 2994-3010.
- Guccione E, Hitchcock A, Hall SJ, Mulholland F, Shearer N, van Vliet AHM & Kelly DJ (2010) Reduction of fumarate, mesaconate and crotonate by Mfr, a novel oxygen-regulated periplasmic reductase in Campylobacter jejuni.. Environ Microbiol, 12(3), 576-591.
- Smart JP, Cliff MJ & Kelly DJ (2009) A role for tungsten in the biology of Campylobacter jejuni: tungstate stimulates formate dehydrogenase activity and is transported via an ultra-high affinity ABC system distinct from the molybdate transporter.. Mol Microbiol, 74(3), 742-757.
- Atack JM & Kelly DJ (2009) Oxidative stress in Campylobacter jejuni: responses, resistance and regulation.. Future Microbiol, 4(6), 677-690.
- Mulligan C, Geertsma ER, Severi E, Kelly DJ, Poolman B & Thomas GH (2009) The substrate-binding protein imposes directionality on an electrochemical sodium gradient-driven TRAP transporter. P NATL ACAD SCI USA, 106(6), 1778-1783.
- Wright JA, Grant AJ, Hurd D, Harrison M, Guccione EJ, Kelly DJ & Maskell DJ (2009) Metabolite and transcriptome analysis of Campylobacter jejuni in vitro growth reveals a stationary-phase physiological switch. MICROBIOL-SGM, 155, 80-94.
- Hall SJ, Hitchcock A, Butler CS & Kelly DJ (2008) A Multicopper oxidase (Cj1516) and a CopA homologue (Cj1161) are major components of the copper homeostasis system of Campylobacter jejuni.. J Bacteriol, 190(24), 8075-8085.
- Atack JM, Harvey P, Jones MA & Kelly DJ (2008) The Campylobacter jejuni thiol peroxidases Tpx and Bcp both contribute to aerotolerance and peroxide-mediated stress resistance but have distinct substrate specificities.. J Bacteriol, 190(15), 5279-5290.
- Atack JM & Kelly DJ (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(Pt 8), 2219-2230.
- Guccione E, Leon-Kempis MDR, Pearson BM, Hitchin E, Mulholland F, van Diemen PM, Stevens MP & Kelly DJ (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.. Mol Microbiol, 69(1), 77-93.
- Pajaniappan M, Hall JE, Cawthraw SA, Newell DG, Gaynor EC, Fields JA, Rathbun KM, Agee WA, Burns CM, Hall SJ, Kelly DJ & Thompson SA (2008) A temperature-regulated Campylobacter jejuni gluconate dehydrogenase is involved in respiration-dependent energy conservation and chicken colonization. MOL MICROBIOL, 68(2), 474-491.