Helicobacter pylori Outer Membrane Vesicle Size Determines Their Mechanisms of Host Cell Entry and Protein Content
Gram-negative pathogens ubiquitously shed outer membrane vesicles (OMVs) that play a central role in initiating and regulating pathogenesis in the host. Due to their highly inflammatory nature, OMVs are extensively being examined for their role in mediating disease in addition to their applications...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01466/full |
| _version_ | 1818250002696241152 |
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| author | Lorinda Turner Natalie J. Bitto Natalie J. Bitto David L. Steer Camden Lo Kimberley D’Costa Georg Ramm Georg Ramm Mitch Shambrook Mitch Shambrook Andrew F. Hill Andrew F. Hill Richard L. Ferrero Richard L. Ferrero Maria Kaparakis-Liaskos Maria Kaparakis-Liaskos Maria Kaparakis-Liaskos |
| author_facet | Lorinda Turner Natalie J. Bitto Natalie J. Bitto David L. Steer Camden Lo Kimberley D’Costa Georg Ramm Georg Ramm Mitch Shambrook Mitch Shambrook Andrew F. Hill Andrew F. Hill Richard L. Ferrero Richard L. Ferrero Maria Kaparakis-Liaskos Maria Kaparakis-Liaskos Maria Kaparakis-Liaskos |
| author_sort | Lorinda Turner |
| collection | DOAJ |
| description | Gram-negative pathogens ubiquitously shed outer membrane vesicles (OMVs) that play a central role in initiating and regulating pathogenesis in the host. Due to their highly inflammatory nature, OMVs are extensively being examined for their role in mediating disease in addition to their applications in innovative vaccines. A key mechanism whereby OMVs mediate inflammation and disease progression is dependent on their ability to enter host cells. Currently, the role of OMV size on determining their mechanism of cellular entry and their protein composition remains unknown. In this study, we examined the mechanisms whereby OMV size regulates their mode of entry into epithelial cells, in addition to their protein cargo and composition. We identified that a heterogeneous sized population of Helicobacter pylori OMVs entered epithelial cells via macropinocytosis, clathrin, and caveolin-dependent endocytosis. However, smaller OMVs ranging from 20 to 100 nm in size preferentially entered host cells via caveolin-mediated endocytosis. Whereas larger OMVs ranging between 90 and 450 nm in size entered host epithelial cells via macropinocytosis and endocytosis. Most importantly, we identified the previously unknown contribution that OMV size has on determining their protein content, as fewer and less diverse bacterial proteins were contained within small OMVs compared to larger OMVs. Collectively, these findings identify the importance of OMV size in determining the mechanisms of OMV entry into host cells, in addition to regulating their protein cargo, composition, and subsequent immunogenicity. These findings have significant implications in broadening our understanding of the bacterial regulation of virulence determinants and immunogenic proteins associated with OMVs, their role in mediating pathogenesis and in refining the design and development of OMV-based vaccines. |
| first_indexed | 2024-12-12T15:45:28Z |
| format | Article |
| id | doaj.art-b6cf2b589ef0431c8516f14253d4f2e8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T15:45:28Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b6cf2b589ef0431c8516f14253d4f2e82022-12-22T00:19:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-07-01910.3389/fimmu.2018.01466373147Helicobacter pylori Outer Membrane Vesicle Size Determines Their Mechanisms of Host Cell Entry and Protein ContentLorinda Turner0Natalie J. Bitto1Natalie J. Bitto2David L. Steer3Camden Lo4Kimberley D’Costa5Georg Ramm6Georg Ramm7Mitch Shambrook8Mitch Shambrook9Andrew F. Hill10Andrew F. Hill11Richard L. Ferrero12Richard L. Ferrero13Maria Kaparakis-Liaskos14Maria Kaparakis-Liaskos15Maria Kaparakis-Liaskos16Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Melbourne, VIC, AustraliaDepartment of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC, AustraliaResearch Centre for Extracellular Vesicles, School of Molecular Sciences, La Trobe University, Melbourne, VIC, AustraliaMonash University, Clayton, VIC, AustraliaMonash Micro Imaging, Monash University, Clayton, VIC, AustraliaCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Melbourne, VIC, AustraliaMonash Biomedical Proteomics Facility, Monash University, Clayton, VIC, AustraliaDepartment of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, AustraliaResearch Centre for Extracellular Vesicles, School of Molecular Sciences, La Trobe University, Melbourne, VIC, AustraliaLa Trobe Institute for Molecular Sciences, La Trobe University, Melbourne, VIC, AustraliaResearch Centre for Extracellular Vesicles, School of Molecular Sciences, La Trobe University, Melbourne, VIC, AustraliaLa Trobe Institute for Molecular Sciences, La Trobe University, Melbourne, VIC, AustraliaCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Melbourne, VIC, AustraliaDepartment of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, AustraliaCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Melbourne, VIC, AustraliaDepartment of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC, AustraliaResearch Centre for Extracellular Vesicles, School of Molecular Sciences, La Trobe University, Melbourne, VIC, AustraliaGram-negative pathogens ubiquitously shed outer membrane vesicles (OMVs) that play a central role in initiating and regulating pathogenesis in the host. Due to their highly inflammatory nature, OMVs are extensively being examined for their role in mediating disease in addition to their applications in innovative vaccines. A key mechanism whereby OMVs mediate inflammation and disease progression is dependent on their ability to enter host cells. Currently, the role of OMV size on determining their mechanism of cellular entry and their protein composition remains unknown. In this study, we examined the mechanisms whereby OMV size regulates their mode of entry into epithelial cells, in addition to their protein cargo and composition. We identified that a heterogeneous sized population of Helicobacter pylori OMVs entered epithelial cells via macropinocytosis, clathrin, and caveolin-dependent endocytosis. However, smaller OMVs ranging from 20 to 100 nm in size preferentially entered host cells via caveolin-mediated endocytosis. Whereas larger OMVs ranging between 90 and 450 nm in size entered host epithelial cells via macropinocytosis and endocytosis. Most importantly, we identified the previously unknown contribution that OMV size has on determining their protein content, as fewer and less diverse bacterial proteins were contained within small OMVs compared to larger OMVs. Collectively, these findings identify the importance of OMV size in determining the mechanisms of OMV entry into host cells, in addition to regulating their protein cargo, composition, and subsequent immunogenicity. These findings have significant implications in broadening our understanding of the bacterial regulation of virulence determinants and immunogenic proteins associated with OMVs, their role in mediating pathogenesis and in refining the design and development of OMV-based vaccines.https://www.frontiersin.org/article/10.3389/fimmu.2018.01466/fullbacterial membrane vesiclesendocytosismacropinocytosispathogenesisproteomicsouter membrane vesicles |
| spellingShingle | Lorinda Turner Natalie J. Bitto Natalie J. Bitto David L. Steer Camden Lo Kimberley D’Costa Georg Ramm Georg Ramm Mitch Shambrook Mitch Shambrook Andrew F. Hill Andrew F. Hill Richard L. Ferrero Richard L. Ferrero Maria Kaparakis-Liaskos Maria Kaparakis-Liaskos Maria Kaparakis-Liaskos Helicobacter pylori Outer Membrane Vesicle Size Determines Their Mechanisms of Host Cell Entry and Protein Content Frontiers in Immunology bacterial membrane vesicles endocytosis macropinocytosis pathogenesis proteomics outer membrane vesicles |
| title | Helicobacter pylori Outer Membrane Vesicle Size Determines Their Mechanisms of Host Cell Entry and Protein Content |
| title_full | Helicobacter pylori Outer Membrane Vesicle Size Determines Their Mechanisms of Host Cell Entry and Protein Content |
| title_fullStr | Helicobacter pylori Outer Membrane Vesicle Size Determines Their Mechanisms of Host Cell Entry and Protein Content |
| title_full_unstemmed | Helicobacter pylori Outer Membrane Vesicle Size Determines Their Mechanisms of Host Cell Entry and Protein Content |
| title_short | Helicobacter pylori Outer Membrane Vesicle Size Determines Their Mechanisms of Host Cell Entry and Protein Content |
| title_sort | helicobacter pylori outer membrane vesicle size determines their mechanisms of host cell entry and protein content |
| topic | bacterial membrane vesicles endocytosis macropinocytosis pathogenesis proteomics outer membrane vesicles |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01466/full |
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