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SHR Neuro Cancer Cardio Metab Microb Lipid

Comparative Analysis of Campylobacter fetus virulence mechanisms

Abstract: The bacterial species Campylobacter fetus is a significant animal pathogen, causing epidemic abortion and infertility in cattle. It is also an important human pathogen causing septicaemia, putting predominantly immunocompromised people at risk. Very little is understood about C. fetus virulence mechanisms and the interaction with its hosts. C. fetus consists of two subspecies, C. fetus subsp. fetus und C. fetus subsp. venerealis, which are extraordinarily closely related on the genetic level but exhibit striking differences in tissue and host specificity. Comparative analysis of these subspecies thus provides an excellent model to understand the molecular nature of this pathogens host and tissue tropism and to elucidate the molecular interactions with its host cells. We have compared the genomes of the subspecies and identified genome segments unique to each with a putative role in pathogenicity. These include a type IV macromolecular transport system (T4SS) typically involved in secretion of bacterial virulence proteins to eukaryotic host cells, and an enzyme linking LPS biosynthesis and structure to environmental cues. This research aims to determine the contribution of specific genes to the host tropism and virulence of C. fetus subspecies. To do so we require much more detailed understanding of the natural appearance of the C. fetus infection process. We propose a thorough histopathological analysis of infected tissues derived from the veterinary field. Insights gained here will be enhanced by fine resolution of host-pathogen interactions on the cellular level. C.fetus susceptible in vitro models of cultured animal and human cells will be developed to assess the functional contribution of putative virulence genes to stages of the C. fetus infection process. Techniques developed in this project should differentiate involvement of the virulence genes in bacterial adherence, cellular entry, proinflammatory activation of host cells, chemokine secretion and cytotoxicity. The important applications of these models will be not only to compare the divergent virulence properties of the C. fetus subspecies but to evaluate phenotypic differences in host-pathogen interactions following mutagenesis of putative virulence genes. We have established a new series of genetics tools for this organism which enable us to perform mutational analyses readily. These studies will provide much clearer insights into the function of specific genes in determining host preference and the molecular basis of C. fetus pathogenicity.

Keywords: Molecular pathology; bacteriology; medical microbiology

Project Leader:: Gorkiewicz Gregor

Duration:: 01.02.2008-30.09.2012

Programme:: Einzelprojekt

Type of Research: basic research

Staff: Gorkiewicz, Gregor, Project Leader

MUG Research Units: Diagnostic and Research Institute of Pathology

Project partners: Institute for Molecular Biosciences, Austria

Funded by: FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Austria

Project results published: > Molecular Characterization of the Pathogenicity Is... Abstract Book CHRO 2013 published by the Society for General Microbiology. 2013; -17th International Workshop on Campylobacter, Helicobacter and Related Organisms; SEP 15-19; Aberdeen, UK.; > Differental RNA-sequencing (dRNA-seq) of Campyloba... Abstract Book CHRO 2013 published by the Society for General Microbiology. 2013; -17th International Workshop on Campylobacter, Helicobacter and Related Organisms; SEP 15-19; Aberdeen, UK.; > Horizontally acquired genetic elements drive genom... CHRO 2013 Abstract Book published by the Society for General Microbiology. 2013; -17th International Conference on Campylobacter, Helicobacter and Related Organisms; SEP 15-19; Aberdeen, UK.; > Epithelial invasion and pathogenicity of Campyloba... Abstract Book CHRO 2013 published by the Society for General Microbiology. 2013; -17th International Workshop on Campylobacter, Helicobacter and Related Organisms; SEP 15-19; Aberdeen, UK.; > FIDO-family proteins of Campylobacter fetus subspe... Abstract Book CHRO 2013 published by the Society for General Microbiology. 2013; -17th International Workshop on Campylobacter, Helicobacter and Related Organisms; SEP 15-19; Aberdeen, UK.; > Comparative genome analysis identified horizontall... Abstract Book CHRO 2013 published by the Society for General Microbiology. 2012; -17th International Conference on Campylobacter, Helicobacter and Related Organsims; SEP 15-19; Aberdeen, UK.; > New molecular microbiology approaches in the study... Microb Biotechnol. 2011; 4(1): 8-19.; > Interbacterial macromolecular transfer by the Camp... J Bacteriol. 2011; 193(3):744-758; > A genomic island defines subspecies-specific virul... J Bacteriol. 2010; 192(2): 502-517.