Professor Dave Kelly

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)

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.

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.