Glutathione Activates Type III Secretion System Through Vfr in Pseudomonas aeruginosa
Glutathione (GSH) is the most abundant antioxidant in all living organisms. Previously, we have shown that a deletion mutant in the glutathione synthetase gene (ΔgshB) decreases the expression of type III secretion system (T3SS) genes of Pseudomonas aeruginosa. However, the mechanism remains elusive...
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2019.00164/full |
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| author | Yani Zhang Chao Zhang Xiao Du Yun Zhou Weina Kong Gee W. Lau Gukui Chen Gurjeet Singh Kohli Gurjeet Singh Kohli Liang Yang Liang Yang Tietao Wang Haihua Liang |
| author_facet | Yani Zhang Chao Zhang Xiao Du Yun Zhou Weina Kong Gee W. Lau Gukui Chen Gurjeet Singh Kohli Gurjeet Singh Kohli Liang Yang Liang Yang Tietao Wang Haihua Liang |
| author_sort | Yani Zhang |
| collection | DOAJ |
| description | Glutathione (GSH) is the most abundant antioxidant in all living organisms. Previously, we have shown that a deletion mutant in the glutathione synthetase gene (ΔgshB) decreases the expression of type III secretion system (T3SS) genes of Pseudomonas aeruginosa. However, the mechanism remains elusive. In this study, a comprehensive transcriptomic analysis of the GSH-deficient mutant ΔgshAΔgshB was used to elucidate the role of GSH in the pathogenesis of P. aeruginosa. The data show that the expression of genes in T3SS, type VI secretion system (T6SS) and some regulatory genes were impaired. ΔgshAΔgshB was attenuated in a mouse model of acute pneumonia, swimming and swarming motilities, and biofilm formation. Under T3SS inducing conditions, GSH enhanced the expression of T3SS in both wild-type PAO1 and ΔgshAΔgshB, but not in Δvfr. Genetic complementation of Δvfr restored the ability of GSH to induce the expression of T3SS genes. Site-directed mutagenesis based substitution of cysteine residues with alanine in Vfr protein abolished the induction of T3SS genes by GSH, confirming that GSH regulates T3SS genes through Vfr. Exposure to H2O2 decreased free thiol content on Vfr, indicating that the protein was sensitive to redox modification. Importantly, GSH restored the oxidized Vfr to reduced state. Collectively, these results suggest that GSH serves as an intracellular redox signal sensed by Vfr to upregulate T3SS expression in P. aeruginosa. Our work provides new insights into the role of GSH in P. aeruginosa pathogenesis. |
| first_indexed | 2024-12-23T06:14:57Z |
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| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-23T06:14:57Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-1b1e7cfd3c814400b420a8c8d585b7e92022-12-21T17:57:19ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882019-05-01910.3389/fcimb.2019.00164447201Glutathione Activates Type III Secretion System Through Vfr in Pseudomonas aeruginosaYani Zhang0Chao Zhang1Xiao Du2Yun Zhou3Weina Kong4Gee W. Lau5Gukui Chen6Gurjeet Singh Kohli7Gurjeet Singh Kohli8Liang Yang9Liang Yang10Tietao Wang11Haihua Liang12Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an, ChinaDepartment of Pathobiology, University of Illinois at Urbana-Champaign, Champaign, IL, United StatesKey Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an, ChinaSingapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, SingaporeAlfred Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung, Bremerhaven, GermanySingapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, SingaporeSchool of Medicine, Southern University of Science and Technology, Shenzhen, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an, ChinaGlutathione (GSH) is the most abundant antioxidant in all living organisms. Previously, we have shown that a deletion mutant in the glutathione synthetase gene (ΔgshB) decreases the expression of type III secretion system (T3SS) genes of Pseudomonas aeruginosa. However, the mechanism remains elusive. In this study, a comprehensive transcriptomic analysis of the GSH-deficient mutant ΔgshAΔgshB was used to elucidate the role of GSH in the pathogenesis of P. aeruginosa. The data show that the expression of genes in T3SS, type VI secretion system (T6SS) and some regulatory genes were impaired. ΔgshAΔgshB was attenuated in a mouse model of acute pneumonia, swimming and swarming motilities, and biofilm formation. Under T3SS inducing conditions, GSH enhanced the expression of T3SS in both wild-type PAO1 and ΔgshAΔgshB, but not in Δvfr. Genetic complementation of Δvfr restored the ability of GSH to induce the expression of T3SS genes. Site-directed mutagenesis based substitution of cysteine residues with alanine in Vfr protein abolished the induction of T3SS genes by GSH, confirming that GSH regulates T3SS genes through Vfr. Exposure to H2O2 decreased free thiol content on Vfr, indicating that the protein was sensitive to redox modification. Importantly, GSH restored the oxidized Vfr to reduced state. Collectively, these results suggest that GSH serves as an intracellular redox signal sensed by Vfr to upregulate T3SS expression in P. aeruginosa. Our work provides new insights into the role of GSH in P. aeruginosa pathogenesis.https://www.frontiersin.org/article/10.3389/fcimb.2019.00164/fullglutathionetype III secretion systemVfrpathogenicityPseudomonas aeruginosa |
| spellingShingle | Yani Zhang Chao Zhang Xiao Du Yun Zhou Weina Kong Gee W. Lau Gukui Chen Gurjeet Singh Kohli Gurjeet Singh Kohli Liang Yang Liang Yang Tietao Wang Haihua Liang Glutathione Activates Type III Secretion System Through Vfr in Pseudomonas aeruginosa Frontiers in Cellular and Infection Microbiology glutathione type III secretion system Vfr pathogenicity Pseudomonas aeruginosa |
| title | Glutathione Activates Type III Secretion System Through Vfr in Pseudomonas aeruginosa |
| title_full | Glutathione Activates Type III Secretion System Through Vfr in Pseudomonas aeruginosa |
| title_fullStr | Glutathione Activates Type III Secretion System Through Vfr in Pseudomonas aeruginosa |
| title_full_unstemmed | Glutathione Activates Type III Secretion System Through Vfr in Pseudomonas aeruginosa |
| title_short | Glutathione Activates Type III Secretion System Through Vfr in Pseudomonas aeruginosa |
| title_sort | glutathione activates type iii secretion system through vfr in pseudomonas aeruginosa |
| topic | glutathione type III secretion system Vfr pathogenicity Pseudomonas aeruginosa |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2019.00164/full |
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