Insights into the mechanism regulating the differential expression of the P28-OMP outer membrane proteins in obligatory intracellular pathogen Ehrlichia chaffeensis
Autor: | Xiaohui Ma, Zhouyi Chai, Weihui Wu, Yingxing Feng, Fang Bai, Heting Cui, Zhihui Cheng, Zhexuan Wang, Yongxin Jin, Xiaoxiao Li, Yu Cao, Nan Duan, Yasuko Rikihisa, Jiaqi Yan |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Ehrlichiosis Hot Temperature Epidemiology THP-1 Cells 030106 microbiology Immunology Biology Microbiology Tr1 Intracellular pathogen 03 medical and health sciences Ticks Bacterial Proteins Species Specificity Virology parasitic diseases Drug Discovery Consensus Sequence medicine Escherichia coli Ehrlichia chaffeensis Animals Humans Differential expression differential gene expression Promoter Regions Genetic Mechanism (biology) General Medicine P28-OMP outer membrane proteins Gene Expression Regulation Bacterial medicine.disease biology.organism_classification bacterial infections and mycoses human monocytic ehrlichiosis 030104 developmental biology Infectious Diseases Parasitology Bacterial outer membrane Research Article Bacterial Outer Membrane Proteins Transcription Factors |
Zdroj: | Emerging Microbes & Infections article-version (VoR) Version of Record |
ISSN: | 2222-1751 |
Popis: | Ehrlichia chaffeensis causes human monocytic ehrlichiosis (HME), which is one of the most prevalent, life-threatening emerging infectious zoonoses. The life cycle of E. chaffeensis includes ticks and mammals, in which E. chaffeensis proteins are expressed differentially contributing to bacterial survival and infection. Among the E. chaffeensis P28-OMP outer membrane proteins, OMP-1B and P28 are predominantly expressed in tick cells and mammalian macrophages, respectively. The mechanisms regulating this differential expression have not been comprehensively studied. Here, we demonstrate that the transcriptional regulators EcxR and Tr1 regulate the differential expression of omp-1B and p28 in E. chaffeensis. Recombinant E. chaffeensis Tr1 bound to the promoters of omp-1B and p28, and transactivated omp-1B and p28 promoter-EGFP fusion constructs in Escherichia coli. The consensus sequence of Tr1 binding motifs was AC/TTATA as determined with DNase I footprint assay. Tr1 showed a higher affinity towards the p28 promoter than the omp-1B promoter as determined with surface plasmon resonance. EcxR activated the tr1 expression in response to a temperature decrease. At 37°C low level of Tr1 activated the p28 expression. At 25°C high level of Tr1 activated the omp-1B expression, while repressing the p28 expression by binding to an additional site upstream of the p28 gene. Our data provide insights into a novel mechanism mediated by Tr1 regulating E. chaffeensis differential gene expression, which may aid in the development of new therapeutics for HME. |
Databáze: | OpenAIRE |
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