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NrtR Mediated Regulation of H1-T6SS in Pseudomonas aeruginosa
NrtR is a Nudix-related transcriptional regulator that is distributed among diverse bacteria and plays an important role in modulating bacterial intracellular NAD homeostasis. Previously, we showed that NrtR influences the T3SS expression and pathogenesis of Pseudomonas aeruginosa and demonstrated t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865458/ https://www.ncbi.nlm.nih.gov/pubmed/35196795 http://dx.doi.org/10.1128/spectrum.01858-21 |
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author | Zhang, Xinxin Yin, Liwen Liu, Qi Wang, Dan Xu, Congjuan Pan, Xiaolei Bai, Fang Cheng, Zhihui Wu, Weihui Jin, Yongxin |
author_facet | Zhang, Xinxin Yin, Liwen Liu, Qi Wang, Dan Xu, Congjuan Pan, Xiaolei Bai, Fang Cheng, Zhihui Wu, Weihui Jin, Yongxin |
author_sort | Zhang, Xinxin |
collection | PubMed |
description | NrtR is a Nudix-related transcriptional regulator that is distributed among diverse bacteria and plays an important role in modulating bacterial intracellular NAD homeostasis. Previously, we showed that NrtR influences the T3SS expression and pathogenesis of Pseudomonas aeruginosa and demonstrated that NrtR mediates T3SS regulation through the cAMP/Vfr pathway. In the present study, we found that mutation of the nrtR gene leads to upregulation of the Hcp secretion island-I type VI secretion system (H1-T6SS). Further analysis revealed that mutation of the nrtR gene results in upregulation of regulatory RNAs (RsmY/RsmZ) that are known to control the H1-T6SS by sequestration of RsmA or RsmN. Simultaneous deletion of rsmY/rsmZ reduced the expression of H1-T6SS in the ΔnrtR mutant. In addition, overexpression of either rsmA or rsmN in ΔnrtR decreased H1-T6SS expression. Chromatin immunoprecipitation (ChIP)-Seq and electrophoretic mobility shift assay (EMSA) analyses revealed that NrtR directly binds to the promoters of rsmY, rsmZ and tssA1 (first gene of the H1-T6SS operon). Overall, the results from this study reveal the molecular details of NrtR-mediated regulation of H1-T6SS in P. aeruginosa. IMPORTANCE NrtR is a Nudix-related transcriptional regulator and controls the NAD cofactor biosynthesis in bacteria. P. aeruginosa NrtR binds to the intergenic region between nadD2 and pcnA to repress the expression of the two operons, therefore controlling the NAD biosynthesis. We have previously reported that NrtR controls T3SS expression via the cAMP/Vfr pathway in P. aeruginosa. However, the global regulatory function and direct binding targets of the NrtR remain elusive in P. aeruginosa. This study reveals novel direct regulatory targets of the NrtR in P. aeruginosa, elucidating the molecular mechanism of NrtR-mediated regulation of H1-T6SS. |
format | Online Article Text |
id | pubmed-8865458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-88654582022-03-04 NrtR Mediated Regulation of H1-T6SS in Pseudomonas aeruginosa Zhang, Xinxin Yin, Liwen Liu, Qi Wang, Dan Xu, Congjuan Pan, Xiaolei Bai, Fang Cheng, Zhihui Wu, Weihui Jin, Yongxin Microbiol Spectr Research Article NrtR is a Nudix-related transcriptional regulator that is distributed among diverse bacteria and plays an important role in modulating bacterial intracellular NAD homeostasis. Previously, we showed that NrtR influences the T3SS expression and pathogenesis of Pseudomonas aeruginosa and demonstrated that NrtR mediates T3SS regulation through the cAMP/Vfr pathway. In the present study, we found that mutation of the nrtR gene leads to upregulation of the Hcp secretion island-I type VI secretion system (H1-T6SS). Further analysis revealed that mutation of the nrtR gene results in upregulation of regulatory RNAs (RsmY/RsmZ) that are known to control the H1-T6SS by sequestration of RsmA or RsmN. Simultaneous deletion of rsmY/rsmZ reduced the expression of H1-T6SS in the ΔnrtR mutant. In addition, overexpression of either rsmA or rsmN in ΔnrtR decreased H1-T6SS expression. Chromatin immunoprecipitation (ChIP)-Seq and electrophoretic mobility shift assay (EMSA) analyses revealed that NrtR directly binds to the promoters of rsmY, rsmZ and tssA1 (first gene of the H1-T6SS operon). Overall, the results from this study reveal the molecular details of NrtR-mediated regulation of H1-T6SS in P. aeruginosa. IMPORTANCE NrtR is a Nudix-related transcriptional regulator and controls the NAD cofactor biosynthesis in bacteria. P. aeruginosa NrtR binds to the intergenic region between nadD2 and pcnA to repress the expression of the two operons, therefore controlling the NAD biosynthesis. We have previously reported that NrtR controls T3SS expression via the cAMP/Vfr pathway in P. aeruginosa. However, the global regulatory function and direct binding targets of the NrtR remain elusive in P. aeruginosa. This study reveals novel direct regulatory targets of the NrtR in P. aeruginosa, elucidating the molecular mechanism of NrtR-mediated regulation of H1-T6SS. American Society for Microbiology 2022-02-23 /pmc/articles/PMC8865458/ /pubmed/35196795 http://dx.doi.org/10.1128/spectrum.01858-21 Text en Copyright © 2022 Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Zhang, Xinxin Yin, Liwen Liu, Qi Wang, Dan Xu, Congjuan Pan, Xiaolei Bai, Fang Cheng, Zhihui Wu, Weihui Jin, Yongxin NrtR Mediated Regulation of H1-T6SS in Pseudomonas aeruginosa |
title | NrtR Mediated Regulation of H1-T6SS in Pseudomonas aeruginosa |
title_full | NrtR Mediated Regulation of H1-T6SS in Pseudomonas aeruginosa |
title_fullStr | NrtR Mediated Regulation of H1-T6SS in Pseudomonas aeruginosa |
title_full_unstemmed | NrtR Mediated Regulation of H1-T6SS in Pseudomonas aeruginosa |
title_short | NrtR Mediated Regulation of H1-T6SS in Pseudomonas aeruginosa |
title_sort | nrtr mediated regulation of h1-t6ss in pseudomonas aeruginosa |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865458/ https://www.ncbi.nlm.nih.gov/pubmed/35196795 http://dx.doi.org/10.1128/spectrum.01858-21 |
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