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PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids

During infection of a host, Pseudomonas aeruginosa orchestrates global gene expression to adapt to the host environment and counter the immune attacks. P. aeruginosa harbours hundreds of regulatory genes that play essential roles in controlling gene expression. However, their contributions to the ba...

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Autores principales: Pan, Xiaolei, Fan, Zheng, Chen, Lei, Liu, Chang, Bai, Fang, Wei, Yu, Tian, Zhenyang, Dong, Yuanyuan, Shi, Jing, Chen, Hao, Jin, Yongxin, Cheng, Zhihui, Jin, Shouguang, Lin, Jianping, Wu, Weihui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293031/
https://www.ncbi.nlm.nih.gov/pubmed/32406921
http://dx.doi.org/10.1093/nar/gkaa377
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author Pan, Xiaolei
Fan, Zheng
Chen, Lei
Liu, Chang
Bai, Fang
Wei, Yu
Tian, Zhenyang
Dong, Yuanyuan
Shi, Jing
Chen, Hao
Jin, Yongxin
Cheng, Zhihui
Jin, Shouguang
Lin, Jianping
Wu, Weihui
author_facet Pan, Xiaolei
Fan, Zheng
Chen, Lei
Liu, Chang
Bai, Fang
Wei, Yu
Tian, Zhenyang
Dong, Yuanyuan
Shi, Jing
Chen, Hao
Jin, Yongxin
Cheng, Zhihui
Jin, Shouguang
Lin, Jianping
Wu, Weihui
author_sort Pan, Xiaolei
collection PubMed
description During infection of a host, Pseudomonas aeruginosa orchestrates global gene expression to adapt to the host environment and counter the immune attacks. P. aeruginosa harbours hundreds of regulatory genes that play essential roles in controlling gene expression. However, their contributions to the bacterial pathogenesis remain largely unknown. In this study, we analysed the transcriptomic profile of P. aeruginosa cells isolated from lungs of infected mice and examined the roles of upregulated regulatory genes in bacterial virulence. Mutation of a novel regulatory gene pvrA (PA2957) attenuated the bacterial virulence in an acute pneumonia model. Chromatin immunoprecipitation (ChIP)-Seq and genetic analyses revealed that PvrA directly regulates genes involved in phosphatidylcholine utilization and fatty acid catabolism. Mutation of the pvrA resulted in defective bacterial growth when phosphatidylcholine or palmitic acid was used as the sole carbon source. We further demonstrated that palmitoyl coenzyme A is a ligand for the PvrA, enhancing the binding affinity of PvrA to its target promoters. An arginine residue at position 136 was found to be essential for PvrA to bind palmitoyl coenzyme A. Overall, our results revealed a novel regulatory pathway that controls genes involved in phosphatidylcholine and fatty acid utilization and contributes to the bacterial virulence.
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spelling pubmed-72930312020-06-17 PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids Pan, Xiaolei Fan, Zheng Chen, Lei Liu, Chang Bai, Fang Wei, Yu Tian, Zhenyang Dong, Yuanyuan Shi, Jing Chen, Hao Jin, Yongxin Cheng, Zhihui Jin, Shouguang Lin, Jianping Wu, Weihui Nucleic Acids Res Gene regulation, Chromatin and Epigenetics During infection of a host, Pseudomonas aeruginosa orchestrates global gene expression to adapt to the host environment and counter the immune attacks. P. aeruginosa harbours hundreds of regulatory genes that play essential roles in controlling gene expression. However, their contributions to the bacterial pathogenesis remain largely unknown. In this study, we analysed the transcriptomic profile of P. aeruginosa cells isolated from lungs of infected mice and examined the roles of upregulated regulatory genes in bacterial virulence. Mutation of a novel regulatory gene pvrA (PA2957) attenuated the bacterial virulence in an acute pneumonia model. Chromatin immunoprecipitation (ChIP)-Seq and genetic analyses revealed that PvrA directly regulates genes involved in phosphatidylcholine utilization and fatty acid catabolism. Mutation of the pvrA resulted in defective bacterial growth when phosphatidylcholine or palmitic acid was used as the sole carbon source. We further demonstrated that palmitoyl coenzyme A is a ligand for the PvrA, enhancing the binding affinity of PvrA to its target promoters. An arginine residue at position 136 was found to be essential for PvrA to bind palmitoyl coenzyme A. Overall, our results revealed a novel regulatory pathway that controls genes involved in phosphatidylcholine and fatty acid utilization and contributes to the bacterial virulence. Oxford University Press 2020-06-19 2020-05-14 /pmc/articles/PMC7293031/ /pubmed/32406921 http://dx.doi.org/10.1093/nar/gkaa377 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Pan, Xiaolei
Fan, Zheng
Chen, Lei
Liu, Chang
Bai, Fang
Wei, Yu
Tian, Zhenyang
Dong, Yuanyuan
Shi, Jing
Chen, Hao
Jin, Yongxin
Cheng, Zhihui
Jin, Shouguang
Lin, Jianping
Wu, Weihui
PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids
title PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids
title_full PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids
title_fullStr PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids
title_full_unstemmed PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids
title_short PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids
title_sort pvra is a novel regulator that contributes to pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293031/
https://www.ncbi.nlm.nih.gov/pubmed/32406921
http://dx.doi.org/10.1093/nar/gkaa377
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