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MECHANISMS BEHIND HOST-SPECIFICITY OF BACTERIA, INVESTIGATED BY USE OF HOST-SPECIFIC SALMONELLA SEROTYPES

Objective



Host-specific bacteria cause economically important diseases in all production animals to the detriment of production economy and the welfare of the animals. The mechanisms responsible for the host-specificity are only poorly understood, and due to the lack of knowledge, it has never been possibly to evaluate, if host-specificity factors can be utilized for specific prevention and control of diseases.
Salmonellosis is currently the most important zoonosis within EU. Host-speciflc Salmonella serotypes cause economically important diseases in all common productions animals, as well as life threatening, systemic human salmonellosis. In the present project, a systematic investigation will be conducted into the molecular mechanisms behind the.host-specificity of host-specific Salmonella serotypes, i.e. S. dublin, S. gallinarum, S.abortusovis, and S. choleraesuis. The project has 6 participants two of which have one subcontractor each. The overall objective is to establish the basis for utilizing host-range determining factors of bacteria as a means for Controlling disease at the pre-harvbst level, and to investigate if host-specific Salmonella are good candidates as vectors in live vaccine constructs. In sub-project 1(4 tasks with 8 sub-tasks), the specific objectives are to describe the biology of the host-specificity, and to investigate if the host-immune response towards a hostspecific serotype is different in the host to which it is adapted compared with other animals. Challenge experiments in cattle, pigs, sheep and poultry, and assays with cell- and tissue cultures from the sarne animals, are employed. Specific tasks aim to identify the stages during infection where the host-specific phenotypes are expressed, to investigate if the serotype specific virulence plasmids are important for hostspecificity, and to investigate if challenged animals are protected against challenge with the other hostspecific serotypes. In sub-project 2 (6 tasks with 2 sub-tasks), molecular methods are used to identify and characterize the factor(s) responsible for host-specificity of the host-specific Salmonella serotypes. The factors can be traits of the bacteria as well as of the host, and are probably different for the different serotypes. Factors are identified from studies of mutant and recombinant strains that show an altered hostrestriction phenotype. Characterization of the factors include identification of the relevant DNAfragments, mapping of the fragments, genetic analysis of the nature of mutations, identification of the relevant genes, sequence and expression analysis and analysis of the ability of the DNA to change the host-specificity of other host-specific Salmonella serotypes. In sub-project 3 (2 tasks), the ability of S.
abortusovis to act as a vector for heterologaus antigen presentation in a live vaccine is investigated. The gene for E. coli maltose binding protein (MalE) is cloned into the attenuated strain Rv6 and the immune response towards this protein is measured in mice and sheep. Next, small fragments of CAEV-virus (Caprine Arthritis Encephalitis Virus) genome is cloned into the male and the protective ability of these antigens are measured by challenge with the virus. The project is carried out over a four years period. Major deliverables will be in the form of publication in international journals from all sub-project, sets of well characterized strains with different genetic manipulations, and which will be in the public domain, a quantitative assay for measurement of cytokine profiles, fragments of DNA encoding one or more factors that are responsible for host-specificity, an evaluation report on the possible use of host-restriction factors in control of diseases, and an evaluation reports on the possible use of host-specific serotypes as carriers of heterologous antigens. Commercialization will be considered before publication of results.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

THE ROYAL VETERINARY AND AGRICULTURAL UNIVERSITY
Address
Bülowsvej, 13
1879 Frederiksberg C
Denmark

Participants (5)

BBSRC Institute for Animal Health
United Kingdom
Address
Compton Laboratory Compton
RG16 0NN Newbury
I.N.R.A. - CENTRE DE RECHERCHE DE TOURS-NOUZILLY
France
Address

37380 Nouzilly
Istituto Zooprofilattico Sperimentale della Sardegna G. Pegreffi
Italy
Address
Via Duca Degli Abruzzi 8
07100 Sassari
UNIVERSIDAD DE SEVILLA
Spain
Address
Apartado 1095
41080 Sevilla
Università degli Studi di Sassari
Italy
Address
Viale San Pietro 43/B
07100 Sassari