Abstract
BackgroundCoxiella burnetii is the causative agent of the zoonotic disease Q fever. As it is an intracellular pathogen, infection by C. burnetii requires adaptation to its eukaryotic host and intracellular environment. The recently developed cell-free medium also allows the bacteria to propagate without host cells, maintaining its infection potential. The adaptation to different hosts or extracellular environments has been assumed to involve genome-wide modulation of C. burnetii gene expression. However, little is currently known about these adaptation events which are critical for understanding the intracellular survival of C. burnetii.ResultsWe studied C. burnetii genome–wide transcriptional patterns in vivo (mice spleen) and in cell and cell-free in vitro culture models to examine its metabolic pathways and virulence associated gene expression patterns that are required to colonize and persist in different environments. Within each model, the gene expression profiles of the Dutch C. burnetii outbreak strain (602) and NM reference strains were largely similar. In contrast, modulation of gene-expression was strongly influenced by the cultivation method, indicating adaptation of the bacterium to available components. Genome–wide expression profiles of C. burnetii from in vitro cell culture were more similar to those seen for in vivo conditions, while gene expression profiles of cell-free culture were more distant to in vivo. Under in vivo conditions, significant alterations of genes involved in metabolism and virulence were identified. We observed that C. burnetii under in vivo conditions predominantly uses glucose as a carbon source (mostly for biosynthetic processes) and fatty acids for energy generation. C. burnetii experienced nutrient limitation and anaerobiosis as major stressors, while phosphate limitation was identified as an important signal for intracellular growth inside eukaryotic host cells. Finally, the in vivo environment significantly induced expression of several virulence genes, including those implicated in LPS synthesis, colonization, host component modulation and DNA repair mechanisms.ConclusionOur study shows that C. burnetii, with its relative small genome, requires only a subset of core gene functions to survive under in vitro conditions, but requires the induction of full repertoire of genes for successful pathogenesis and thriving in harsh environments in vivo.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2143-7) contains supplementary material, which is available to authorized users.
Highlights
Coxiella burnetii is the causative agent of the zoonotic disease Q fever
For the in vivo transcriptome analysis, C. burnetii obtained from infected mice spleens were chosen, as spleens are highly responsive to infections and bacterial colonization in spleen is a good indicator of infectivity and persistence over time [17,18,19, 26]
We determined the global transcriptional patterns of C. burnetii at 20 days p.i, because host immune responses towards bacterial infection were high around this period allowing us to examine bacterial metabolic adaptations, role of virulence factors and mechanisms to evade host defenses
Summary
Coxiella burnetii is the causative agent of the zoonotic disease Q fever As it is an intracellular pathogen, infection by C. burnetii requires adaptation to its eukaryotic host and intracellular environment. The main clinical manifestation of Q fever in goats and sheep are abortions, which result in the shedding of large numbers of bacteria into the environment. Inhalation of such contaminated aerosols is the main route of transmission in humans and can lead to acute or chronic Q fever [1, 4]. An unprecedented outbreak of Q fever occurred in the Netherlands during the years 2007–2010, with more than 4000 human cases registered; infected dairy goats and sheep were identified as the primary source of the disease [7,8,9,10,11]
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