Fatty acid metabolism and its regulation are known to play important roles in bacteria and eukaryotes. By contrast, although certain archaea appear to metabolize fatty acids, the regulation of the underlying pathways in these organisms remains unclear. Here, we show that a TetR-family transcriptional regulator (FadR Sa ) is involved in regulation of fatty acid metabolism in the crenarchaeon Sulfolobus acidocaldarius . Functional and structural analyses show that FadR Sa binds to DNA at semi-palindromic recognition sites in two distinct stoichiometric binding modes depending on the operator sequence. Genome-wide transcriptomic and chromatin immunoprecipitation analyses demonstrate that the protein binds to only four genomic sites, acting as a repressor of a 30-kb gene cluster comprising 23 open reading frames encoding lipases and β-oxidation enzymes. Fatty acyl-CoA molecules cause dissociation of FadR Sa binding by inducing conformational changes in the protein. Our results indicate that, despite its similarity in overall structure to bacterial TetR-family FadR regulators, FadR Sa displays a different acyl-CoA binding mode and a distinct regulatory mechanism.
Exposure to UV light can result in severe DNA damage. The alternative general transcription factor (GTF) TFB3 has been proposed to play a key role in the UV stress response in the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. Reporter gene assays confirmed that tfb3 is upregulated 90–180 min after UV treatment. In vivo tagging and immunodetection of TFB3 confirmed the induced expression at 90 min. Analysis of a tfb3 insertion mutant showed that genes encoding proteins of the Ups pili and the Ced DNA importer are no longer induced in a tfb3 insertion mutant after UV treatment, which was confirmed by aggregation assays. Thus, TFB3 plays a crucial role in the activation of these genes. Genome wide transcriptome analysis allowed a differentiation between a TFB3-dependent and a TFB3-independent early UV response. The TFB3-dependent UV response is characterized by the early induction of TFB3, followed by TFB3-dependent expression of genes involved in e.g. Ups pili formation and the Ced DNA importer. Many genes were downregulated in the tfb3 insertion mutant confirming the hypothesis that TFB3 acts as an activator of transcription. The TFB3-independent UV response includes the repression of nucleotide metabolism, replication and cell cycle progression in order to allow DNA repair.
Bacteria, as well as eukaryotes, principally fungi, of the upper respiratory tract play key roles in the etiopathogenesis of respiratory diseases, whereas the potential role of archaea remains poorly understood. In this review, we discuss the contribution of all three domains of cellular life to human naso- and oropharyngeal microbiomes, i.e., bacterial microbiota, eukaryotes (mostly fungi), as well as the archaeome and their relation to respiratory and atopic disorders in infancy and adolescence. With this review, we aim to summarize state-of-the-art contributions to the field published in the last decade. In particular, we intend to build bridges between basic and clinical science.
Respiratory viruses play an important role in asthma exacerbation, and early exposure can be involved in recurrent bronchitis and the development of asthma. The exact mechanism is not fully clarified, and pathogen-to-host interaction studies are warranted to identify biomarkers of exacerbation in the early phase. Only a limited number of international exacerbation cohorts were studied. Here, we have established a local pediatric exacerbation study in Germany consisting of children with asthma or chronic, recurrent bronchitis and analyzed the viriome within the nasopharyngeal swab specimens derived from the entire cohort (n = 141). Interestingly, 41% of exacerbated children had a positive test result for human rhinovirus (HRV)/human enterovirus (HEV), and 14% were positive for respiratory syncytial virus (RSV). HRV was particularly prevalent in asthmatics (56%), wheezers (50%), and atopic (66%) patients. Lymphocytes were decreased in asthmatics and in HRV-infected subjects, and patients allergic to house dust mites were more susceptible to HRV infection. Our study thus confirms HRV infection as a strong ‘biomarker’ of exacerbated asthma. Further longitudinal studies will show the clinical progress of those children with a history of an RSV or HRV infection. Vaccination strategies and novel treatment guidelines against HRV are urgently needed to protect those high-risk children from a serious course of disease.
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