Development of a Comprehensive MLST Database for Assessment of Campylobacter Risk Factors

Campylobacter is the most common cause of known bacterial infectious intestinal disease in the UK. Although various risk factors for infection, including undercooked poultry or unpasteurised milk have been identified, its epidemiology remains poorly understood. This is because (i) outbreaks are rarely detected, hence the valuable information on sources and transmission routes which is obtained from outbreak investigations is generally lacking, and (ii) Campylobacter genomes are genetically diverse, and unstable, with frequent inter and intragenomic recombination, together with phase variation, which complicates the interpretation of data from many typing methods. However, a suitable typing technique is now available; multilocus sequence typing (MLST). MLST for Campylobacter jejuni, together with a comprehensive internet accessible MLST database (http://pubmlst.org/campylobacter/) was developed with previous DEFRA support (contract number: OZ0604). <P>

MLST offers advantages including 100% typeability, reproducibility, and the straightforward sharing of data via the internet. The Campylobacter MLST database contains 2275 isolates (27th July 2004) and provides a resource for the scientific, public health, and veterinary communities as well as the food industry. The database is curated to ensure quality control, and could be extended to include other Campylobacter species. If it is to continue, and undergo the proposed expansion, this program of work will require further support.
<P>The objectives of the proposed research are to provide a framework to obtain MLST data which will improve our understanding of the contribution made by non-poultry and poultry related risk factors to the burden of human disease. Specifically (i) to convene a multidisciplinary steering group to ensure a representative MLST database is created, (ii) to maintain and expand the Campylobacter MLST and antigen sequence databases and (iii) to analyse these data, employing new statistical and population genetics approaches, to determine quantitatively the risk to human health posed by different possible sources of Campylobacter (including meat in primary production (abattoirs), retail meats, pets, wild birds, and the environment). <P>These data will be compared with MLST data from a representative set of human clinical isolates to measure the risk of human infection which is associated with the different isolation sources.
<P>Expected Outputs/Results: This study will provide a resource to support regional, national and international studies of Campylobacter epidemiology and will ensure an effective foundation for the cooperative and widespread application to Campylobacter of the MLST approach. Internet accessible databases will provide a framework to allow the interpretation of results, for example the probability that a particular sequence type (ST) originates in a particular source will be examined. New and multicollaborative approaches such as this, to attempt to trace the sources of human Campylobacter infection are central to the development of strategies to control this disease. <P>
Policy Relevance: Our research objectives are translational, to apply proven MLST methodology and existing and newly developed models of bacterial population biology and statistics to improve our understanding of Campylobacter epidemiology. Theoretical aspects will be further enhanced during the study, particularly once the representative database has been established. Recent publications from a number of laboratories using Campylobacter MLST confirmed that the approach has been developed to a stage where an opportunity is now available to exploit it to the full. The widespread application of MLST to Campylobacter has been recommended recently, as a top priority (Priority A) by the Food Standards Agency’s "Advisory Committee on the Microbiological Safety of Foods" (Second Report on Campylobacter).