Award details

Integrated genomic and proteomic characterisation of autotransporter proteins of obligate intracellular bacteria C. abortus and L. intracellularis

Reference	BB/E018939/1
Principal Investigator / Supervisor	Dr David Longbottom
Co-Investigators / Co-Supervisors	Dr Alex Lainson, Professor David Smith
Institution	Moredun Research Institute
Department	Vaccines and Diagnostics
Funding type	Research
Value (£)	1,426,854
Status	Completed
Type	Research Grant
Start date	07/01/2008
End date	06/07/2012
Duration	54 months

Abstract

For many bacterial pathogens, proteins of the Type V secretion system play significant roles in pathogen-host interaction in respect of both pathogenicity and immunity. Members of this protein family are present in a wide diversity of bacteria including the obligate intracellular pathogens Chlamydophila abortus and Lawsonia intracellularis. These species' genomes carry contiguous loci comprising multiple proteins resembling Type V proteins which implies that carriage and/or expression may vary both within and among isolates. To test this hypothesis we will take complementary genomic and functional genomic approaches. Genome sequences for both of these pathogens will be subjected to detailed bioinformatics analyses for motifs representing the main subtypes of these proteins. This will refine the analyses carried out so far and identify any other members of this protein family potentially encoded by these genomes. Comparative genome analysis will be carried out at both intra- and inter-species levels by RFLP, genome hybridisation (microarray) and sequence analysis of the Type V loci from several isolates of these two species. To determine whether isolates vary in expression, candidates will be assessed using RT-PCR, proteomics and immunochemical approaches. To broaden the analysis of Type V protein carriage and expression a seroepidemiological survey of host species (sheep and pigs for C. abortus and L. intracellularis, respectively) will be conducted. This project will define whether Type V proteins of these bacteria impart heterogeneity to strains. This will substantially advance understanding of these important endemic livestock pathogens and make a significant contribution to the development of novel vaccines, diagnostics and epidemiological markers. Furthermore, this will add considerably to the understanding of the important Type V family of bacterial proteins.

Summary

Many infectious diseases affect livestock and impact not only on the health and welfare of animals but also on the economic sustainability of our agriculture industry. Among important animal pathogens are some bacteria that live within and are entirely dependent upon host cells. These so-called 'obligate intracellular' bacteria are very difficult to work with hence gaining understanding to aid in improving animal health is very problematic. Since this type of pathogen must infect a host animal to survive they typically develop mechanisms to very efficiently enter and take over host cells and evade the host's defences. Among the obligate intracellular bacteria, Chlamydophila abortus and Lawsonia intracellularis are very highly prevalent in sheep and pigs, respectively. Since such a high proportion of animals are affected, these infections have a considerable effect on animal health, quality of life and productivity. Although vaccines to these pathogens are available these have shortcomings so ultimately, we would like to develop efficient methods to very effectively reduce the effects of these diseases. Since these bacteria are difficult to work with, use of high-technology genomic methods can be very cost-effective and productive ways to improve the understanding of components with important roles in infection and make new developments in controlling disease. Genome sequences provide a wealth of information about pathogens and from this information we have identified a family of components - so-called Type V secretion proteins - which are likely to be involved in causing disease. Analysis of genomes is very informative however this is of greatest value when combined with an understanding of the function of the protein products of genes. We intend to study this family of proteins using computer-based approaches and laboratory methodologies to gain comprehension of these Type V proteins. These proteins are present on the surface of bacteria and, typically, are recognised by host defences and can result in the host activating defences that protect against infection. The ability to vary these proteins can be an important way to 'camouflage' pathogens allowing them to escape from host defences. Both C. abortus and L. intracellularis have many members of these Type V proteins thus we consider it is very likely that the members of this family present on the bacteria surface will vary. By gaining an understanding of how the presence of these proteins varies in each of these species we will be in a position to define the family members that are most important to infection and therefore lead to improved detection, treatment or prevention of these important livestock diseases.

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Animal Health, Immunology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	Combating Endemic Diseases of Farmed Animals Init (CEDFAS) [2006]
Funding Scheme	X – not Funded via a specific Funding Scheme

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