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Characterization of a Bacterial Kinase That Phosphorylates Dihydrosphingosine to Form dhS1P
Like other members of the phylum Bacteroidetes, the oral anaerobe Porphyromonas gingivalis synthesizes a variety of sphingolipids, similar to its human host. Studies have shown that synthesis of these lipids (dihydroceramides [DHCs]) is involved in oxidative stress resistance, the survival of P. gin...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045371/ https://www.ncbi.nlm.nih.gov/pubmed/35286133 http://dx.doi.org/10.1128/spectrum.00002-22 |
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author | Ranjit, Dev K. Moye, Zachary D. Rocha, Fernanda G. Ottenberg, Gregory Nichols, Frank C. Kim, Hey-Min Walker, Alejandro R. Gibson, Frank C. Davey, Mary E. |
author_facet | Ranjit, Dev K. Moye, Zachary D. Rocha, Fernanda G. Ottenberg, Gregory Nichols, Frank C. Kim, Hey-Min Walker, Alejandro R. Gibson, Frank C. Davey, Mary E. |
author_sort | Ranjit, Dev K. |
collection | PubMed |
description | Like other members of the phylum Bacteroidetes, the oral anaerobe Porphyromonas gingivalis synthesizes a variety of sphingolipids, similar to its human host. Studies have shown that synthesis of these lipids (dihydroceramides [DHCs]) is involved in oxidative stress resistance, the survival of P. gingivalis during stationary phase, and immune modulation. Here, we constructed a deletion mutant of P. gingivalis strain W83 with a deletion of the gene encoding DhSphK1, a protein that shows high similarity to a eukaryotic sphingosine kinase, an enzyme that phosphorylates sphingosine to form sphingosine-1-phosphate. Our data show that deletion of the dhSphK1 gene results in a shift in the sphingolipid composition of P. gingivalis cells; specifically, the mutant synthesizes higher levels of phosphoglycerol DHCs (PG-DHCs) than the parent strain W83. Although PG1348 shows high similarity to the eukaryotic sphingosine kinase, we discovered that the PG1348 enzyme is unique, since it preferentially phosphorylates dihydrosphingosine, not sphingosine. Besides changes in lipid composition, the W83 ΔPG1348 mutant displayed a defect in cell division, the biogenesis of outer membrane vesicles (OMVs), and the amount of K antigen capsule. Taken together, we have identified the first bacterial dihydrosphingosine kinase whose activity regulates the lipid profile of P. gingivalis and underlies a regulatory mechanism of immune modulation. IMPORTANCE Sphingoid base phosphates, such as sphingosine-1-phosphate (S1P) and dihydrosphingosine-1-phosphate (dhS1P), act as ligands for S1P receptors, and this interaction is known to play a central role in mediating angiogenesis, vascular stability and permeability, and immune cell migration to sites of inflammation. Studies suggest that a shift in ratio to higher levels of dhS1P in relation to S1P alters downstream signaling cascades due to differential binding and activation of the various S1P receptor isoforms. Specifically, higher levels of dhS1P are thought to be anti-inflammatory. Here, we report on the characterization of a novel kinase in Porphyromonas gingivalis that phosphorylates dihydrosphingosine to form dhS1P. |
format | Online Article Text |
id | pubmed-9045371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-90453712022-04-28 Characterization of a Bacterial Kinase That Phosphorylates Dihydrosphingosine to Form dhS1P Ranjit, Dev K. Moye, Zachary D. Rocha, Fernanda G. Ottenberg, Gregory Nichols, Frank C. Kim, Hey-Min Walker, Alejandro R. Gibson, Frank C. Davey, Mary E. Microbiol Spectr Research Article Like other members of the phylum Bacteroidetes, the oral anaerobe Porphyromonas gingivalis synthesizes a variety of sphingolipids, similar to its human host. Studies have shown that synthesis of these lipids (dihydroceramides [DHCs]) is involved in oxidative stress resistance, the survival of P. gingivalis during stationary phase, and immune modulation. Here, we constructed a deletion mutant of P. gingivalis strain W83 with a deletion of the gene encoding DhSphK1, a protein that shows high similarity to a eukaryotic sphingosine kinase, an enzyme that phosphorylates sphingosine to form sphingosine-1-phosphate. Our data show that deletion of the dhSphK1 gene results in a shift in the sphingolipid composition of P. gingivalis cells; specifically, the mutant synthesizes higher levels of phosphoglycerol DHCs (PG-DHCs) than the parent strain W83. Although PG1348 shows high similarity to the eukaryotic sphingosine kinase, we discovered that the PG1348 enzyme is unique, since it preferentially phosphorylates dihydrosphingosine, not sphingosine. Besides changes in lipid composition, the W83 ΔPG1348 mutant displayed a defect in cell division, the biogenesis of outer membrane vesicles (OMVs), and the amount of K antigen capsule. Taken together, we have identified the first bacterial dihydrosphingosine kinase whose activity regulates the lipid profile of P. gingivalis and underlies a regulatory mechanism of immune modulation. IMPORTANCE Sphingoid base phosphates, such as sphingosine-1-phosphate (S1P) and dihydrosphingosine-1-phosphate (dhS1P), act as ligands for S1P receptors, and this interaction is known to play a central role in mediating angiogenesis, vascular stability and permeability, and immune cell migration to sites of inflammation. Studies suggest that a shift in ratio to higher levels of dhS1P in relation to S1P alters downstream signaling cascades due to differential binding and activation of the various S1P receptor isoforms. Specifically, higher levels of dhS1P are thought to be anti-inflammatory. Here, we report on the characterization of a novel kinase in Porphyromonas gingivalis that phosphorylates dihydrosphingosine to form dhS1P. American Society for Microbiology 2022-03-14 /pmc/articles/PMC9045371/ /pubmed/35286133 http://dx.doi.org/10.1128/spectrum.00002-22 Text en Copyright © 2022 Ranjit 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 Ranjit, Dev K. Moye, Zachary D. Rocha, Fernanda G. Ottenberg, Gregory Nichols, Frank C. Kim, Hey-Min Walker, Alejandro R. Gibson, Frank C. Davey, Mary E. Characterization of a Bacterial Kinase That Phosphorylates Dihydrosphingosine to Form dhS1P |
title | Characterization of a Bacterial Kinase That Phosphorylates Dihydrosphingosine to Form dhS1P |
title_full | Characterization of a Bacterial Kinase That Phosphorylates Dihydrosphingosine to Form dhS1P |
title_fullStr | Characterization of a Bacterial Kinase That Phosphorylates Dihydrosphingosine to Form dhS1P |
title_full_unstemmed | Characterization of a Bacterial Kinase That Phosphorylates Dihydrosphingosine to Form dhS1P |
title_short | Characterization of a Bacterial Kinase That Phosphorylates Dihydrosphingosine to Form dhS1P |
title_sort | characterization of a bacterial kinase that phosphorylates dihydrosphingosine to form dhs1p |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045371/ https://www.ncbi.nlm.nih.gov/pubmed/35286133 http://dx.doi.org/10.1128/spectrum.00002-22 |
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