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Differential gene expression profiles of human pathogenic and non-pathogenic Brucella species within their host cells
Project
Project code: BfR-BIOS-08-1329-485
Contract period: 01.11.2011
- 31.12.2015
Purpose of research: Applied research
Brucellosis is a globally re-emerging zoonosis. The infection is caused by a variety of different Brucella species which are genetically closely related but phenotypically divergent. There are crucial differences in environmental persistence, pathogenicity and host specificity of the pathogens. Gene regulation might be responsible for the apparent contradiction between genotype and phenotypic traits. In the research project, differential transcriptome analysis comparing intramacrophagic B. suis and B. microti which are highly homologous (99.84% genome sequence identity) shall be performed. The two species occur in different animal reservoirs and they essentially differ according to their pathogenicity for humans.
B. microti has been recently described as a new member of the genus Brucella and is the first species that was isolated from habitats outside mammalian hosts. The isolation of B. microti from environmental samples represents an unpredictable risk for men and animals, as this reservoir may be linked to so far unknown modes of transmission. B. microti proved to be more resistant to acidic environments than the classical Brucella species so that the bacteria may survive and persist in food products despite conservation and long-term storage. In addition, this new species was highly virulent in the murine model of infection. However, human infections have not yet been described. Survival rates, both of B. suis and B. microti, in J744 mice macrophages are similar to those in THP-1 human macrophages although only B. suis is currently known to be highly infectious for humans. The adaptation of zoonotic pathogens to various hosts must be due to gene regulation since the genome content does not change.
In the planned study, gene expression profiles will be analyzed using high-throughput total RNA sequencing („RNA Seq'; Illumina/Solexa). In contrast to DNA-microarray hybridization techniques, the transcripts are analyzed without a priori knowledge of their sequences, a broad spectrum of different expression levels may be detected and all transcribed regions of the genome can be mapped. Data analysis will be followed by biological validation based on qPCR and other genetic methods.
The expected results of the study will complement the knowledge deriving from on-going studies of the Federal Institute for Risk Assessment on the virulence of emerging new species of the genus Brucella.
Section overview
Subjects
- Animal health
- Food microbiology
- Toxicology