دورية أكاديمية
Mycobacterium smegmatis PhoU Proteins Have Overlapping Functions in Phosphate Signaling and Are Essential.
| العنوان: | Mycobacterium smegmatis PhoU Proteins Have Overlapping Functions in Phosphate Signaling and Are Essential. |
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| المؤلفون: | Brokaw AM; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, United States., Eide BJ; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, United States., Muradian M; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, United States., Boster JM; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, United States., Tischler AD; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, United States. |
| المصدر: | Frontiers in microbiology [Front Microbiol] 2017 Dec 18; Vol. 8, pp. 2523. Date of Electronic Publication: 2017 Dec 18 (Print Publication: 2017). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101548977 Publication Model: eCollection Cited Medium: Print ISSN: 1664-302X (Print) Linking ISSN: 1664302X NLM ISO Abbreviation: Front Microbiol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Research Foundation |
| مستخلص: | Many bacteria regulate gene expression in response to phosphate availability using a two-component signal transduction system, the activity of which is controlled by interaction with the Pst phosphate specific transporter and a cytoplasmic protein PhoU. Mycobacterium tuberculosis , the causative agent of tuberculosis, requires its phosphate sensing signal transduction system for virulence and antibiotic tolerance, but the molecular mechanisms of phosphate sensing remain poorly characterized. M. smegmatis serves as a model for studying mycobacterial pathogens including M. tuberculosis. M. smegmatis encodes two proteins with similarity to PhoU, but it was unknown if both proteins participated in signal transduction with the phosphate-responsive SenX3-RegX3 two-component system. We constructed phoU single and double deletion mutants and tested expression of genes in the RegX3 regulon. Only the Δ phoU1 Δ phoU2 mutant exhibited constitutive activation of all the RegX3-regulated genes examined, suggesting that M. smegmatis PhoU1 and PhoU2 have overlapping functions in inhibiting activity of the SenX3-RegX3 two-component system when phosphate is readily available. The Δ phoU1 Δ phoU2 mutant also exhibited decreased tolerance to several anti-tubercular drugs. However, a complex plasmid swapping strategy was required to generate the Δ phoU1 Δ phoU2 mutant, suggesting that either phoU1 or phoU2 is essential for in vitro growth of M. smegmatis . Using whole-genome sequencing, we demonstrated that all five of the Δ phoU1 Δ phoU2 mutants we isolated had independent suppressor mutations predicted to disrupt the function of the Pst phosphate transporter, suggesting that in the absence of the PhoU proteins phosphate uptake by the Pst system is toxic. Collectively, our data demonstrate that the two M. smegmatis PhoU orthologs have overlapping functions in both controlling SenX3-RegX3 activity in response to phosphate availability and regulating phosphate transport by the Pst system. Our results suggest that M. smegmatis can serve as a tractable model for further characterization of the molecular mechanism of phosphate sensing in mycobacteria and to screen for compounds that would interfere with signal transduction and thereby increase the efficacy of existing anti-tubercular antibiotics. |
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| معلومات مُعتمدة: | DP2 AI112245 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: PhoU; Pst system; RegX3; antibiotic tolerance; persister; phosphate; polyphosphate; tuberculosis |
| تواريخ الأحداث: | Date Created: 20180113 Latest Revision: 20200930 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5741670 |
| DOI: | 10.3389/fmicb.2017.02523 |
| PMID: | 29326670 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-302X |
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| DOI: | 10.3389/fmicb.2017.02523 |