Insights into the mechanism regulating the differential expression of the P28-OMP outer membrane proteins in obligatory intracellular pathogen Ehrlichia chaffeensis

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 sur...

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Main Authors: Nan Duan, Xiaohui Ma, Heting Cui, Zhexuan Wang, Zhouyi Chai, Jiaqi Yan, Xiaoxiao Li, Yingxing Feng, Yu Cao, Yongxin Jin, Fang Bai, Weihui Wu, Yasuko Rikihisa, Zhihui Cheng
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2021.1899054
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author Nan Duan
Xiaohui Ma
Heting Cui
Zhexuan Wang
Zhouyi Chai
Jiaqi Yan
Xiaoxiao Li
Yingxing Feng
Yu Cao
Yongxin Jin
Fang Bai
Weihui Wu
Yasuko Rikihisa
Zhihui Cheng
author_facet Nan Duan
Xiaohui Ma
Heting Cui
Zhexuan Wang
Zhouyi Chai
Jiaqi Yan
Xiaoxiao Li
Yingxing Feng
Yu Cao
Yongxin Jin
Fang Bai
Weihui Wu
Yasuko Rikihisa
Zhihui Cheng
author_sort Nan Duan
collection DOAJ
description 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.
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spelling doaj-art-a5b4d7c43c964fb0b629b10c0d24dcfd2025-08-20T02:24:43ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512021-01-0110146147110.1080/22221751.2021.1899054Insights into the mechanism regulating the differential expression of the P28-OMP outer membrane proteins in obligatory intracellular pathogen Ehrlichia chaffeensisNan Duan0Xiaohui Ma1Heting Cui2Zhexuan Wang3Zhouyi Chai4Jiaqi Yan5Xiaoxiao Li6Yingxing Feng7Yu Cao8Yongxin Jin9Fang Bai10Weihui Wu11Yasuko Rikihisa12Zhihui Cheng13Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USAKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People’s Republic of ChinaEhrlichia 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.https://www.tandfonline.com/doi/10.1080/22221751.2021.1899054Ehrlichia chaffeensishuman monocytic ehrlichiosisTr1P28-OMP outer membrane proteinsdifferential gene expression
spellingShingle Nan Duan
Xiaohui Ma
Heting Cui
Zhexuan Wang
Zhouyi Chai
Jiaqi Yan
Xiaoxiao Li
Yingxing Feng
Yu Cao
Yongxin Jin
Fang Bai
Weihui Wu
Yasuko Rikihisa
Zhihui Cheng
Insights into the mechanism regulating the differential expression of the P28-OMP outer membrane proteins in obligatory intracellular pathogen Ehrlichia chaffeensis
Emerging Microbes and Infections
Ehrlichia chaffeensis
human monocytic ehrlichiosis
Tr1
P28-OMP outer membrane proteins
differential gene expression
title Insights into the mechanism regulating the differential expression of the P28-OMP outer membrane proteins in obligatory intracellular pathogen Ehrlichia chaffeensis
title_full Insights into the mechanism regulating the differential expression of the P28-OMP outer membrane proteins in obligatory intracellular pathogen Ehrlichia chaffeensis
title_fullStr Insights into the mechanism regulating the differential expression of the P28-OMP outer membrane proteins in obligatory intracellular pathogen Ehrlichia chaffeensis
title_full_unstemmed Insights into the mechanism regulating the differential expression of the P28-OMP outer membrane proteins in obligatory intracellular pathogen Ehrlichia chaffeensis
title_short Insights into the mechanism regulating the differential expression of the P28-OMP outer membrane proteins in obligatory intracellular pathogen Ehrlichia chaffeensis
title_sort insights into the mechanism regulating the differential expression of the p28 omp outer membrane proteins in obligatory intracellular pathogen ehrlichia chaffeensis
topic Ehrlichia chaffeensis
human monocytic ehrlichiosis
Tr1
P28-OMP outer membrane proteins
differential gene expression
url https://www.tandfonline.com/doi/10.1080/22221751.2021.1899054
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