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Temporal Gene Expression Analysis of the intracellular pathogen Brucella melitensis following bovine Peyer's patch infection.

ABSTRACT: In a time course study, we characterized global gene expression profile of B. melitensis infection in bovine Peyer patches in the first 4 h p.i. Statistical analysis of microarray results reveal that 2,356 B. melitensis genes were detected as differentially expressed (z-score p < 0.025) compared with control between 15 min and 4 h post-infection. A group of 1,740 genes that were differentially expressed in at least 4 out of 5 time points was considered the core set of genes that reflect the major changes in B. melitensis gene expression during the early in vivo bovine Peyer’s patch infection and therefore important in understanding key events in the modulation of host response. From this set of 1,740 differentially expressed genes, 925 (53%) were up-regulated and 815 (47%) were down-regulated compared with the in vitro grown culture. These results reflect significant Brucella metabolic modifications and adaptation from an extracellular to an intracellular lifestyle. Specific genes and biological processes identified in this study will further help elucidate how both host and Brucella interact during the early infectious process to the eventual benefit of the pathogen and to the detriment of the naïve host.

ORGANISM(S): Brucella melitensis bv. 1 str. 16M Brucella melitensis

PROVIDER: GSE89053 | GEO | 2017/08/31

SECONDARY ACCESSION(S): PRJNA350161

REPOSITORIES: GEO

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Project description:Brucella dynamically engage macrophages while trafficking to an intracellular replicative niche as macrophages, the first line of innate host defense, attempt to eliminate organisms. Brucella melitensis, B. neotomae, and B. ovis are highly homologous, yet exhibit a range of host pathogenicity and specificity. RAW 264.7 macrophages infected with B. melitensis, and B. ovis exhibit divergent patterns of bacterial persistence and clearance; conversely, B. melitensis and B. neotomae exhibit similar patterns of infection. Evaluating early macrophage interaction with Brucella spp. allows discovery of host entry and intracellular translocation mechanisms, rather than bacterial replication. Microarray analysis of macrophage transcript levels following a 4 hr Brucella spp. infection revealed 130 probe sets altered compared to uninfected macrophages; specifically, 72 probe sets were increased and 58 probe sets were decreased with any Brucella spp. Interestingly, much of the inflammatory response was not regulated by the number of Brucella gaining intracellular entry, as macrophage transcript levels were often equivalent among B. melitensis, B. ovis, and B. neotomae infections. An additional 33 probe sets were identified with altered macrophage transcript levels among Brucella spp. infections that may correlate with species specific host defenses and intracellular survival. Gene ontological categorization unveiled genes altered among species are involved in cell growth and maintenance, response to external stimuli, transcription regulation, transporter activity, endopeptidase inhibitor activity and G-protein mediated signaling. Host transcript profiles provide a foundation to understand variations in Brucella spp. infections, while structure of the macrophage response and intracellular niche of Brucella spp. will be revealed through piecewise consideration of host signaling pathways. Keywords: Macrophage, intracellular pathogen, Brucella melitensis, Brucella neotomae, Brucella ovis, inflammatory immune response, species specificity

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Temporal Gene Expression Analysis of the intracellular pathogen Brucella melitensis following bovine Peyer's patch infection.

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