The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase against <i>Moraxella catarrhalis</i>
Neutrophil elastase (NE) contributes to innate antibacterial defense at both the intracellular (phagocytosis) and extracellular (degranulation, NETosis) levels. <i>Moraxella catarrhalis</i>, a human respiratory pathogen, can exist in an inflammatory milieu which contains NE. No data are...
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6607 |
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| author | Justyna Roszkowiak Siobhán McClean Aleksandra M. Mirończuk Daria Augustyniak |
| author_facet | Justyna Roszkowiak Siobhán McClean Aleksandra M. Mirończuk Daria Augustyniak |
| author_sort | Justyna Roszkowiak |
| collection | DOAJ |
| description | Neutrophil elastase (NE) contributes to innate antibacterial defense at both the intracellular (phagocytosis) and extracellular (degranulation, NETosis) levels. <i>Moraxella catarrhalis</i>, a human respiratory pathogen, can exist in an inflammatory milieu which contains NE. No data are available on the action of NE against <i>M. catarrhalis</i> or on the counteraction of NE-dependent host defenses by this pathogen. Using time-kill assays we found that bacteria are able to survive and replicate in the presence of NE. Transmission electron microscopy and flow cytometry studies with NE-treated bacteria revealed that while NE admittedly destabilizes the outer membrane leaflet, it does not cause cytoplasmic membrane rupture, suggesting that the enzyme does not target components that are essential for cell integrity. Using LC-MS/MS spectroscopy we determined that NE cleaved at least three virulent surface proteins in outer membrane vesicles (OMVs) of <i>M. catarrhalis,</i> including OMP CD, McaP, and TbpA. The cleavage of OMP CD contributes to the significant decrease in resistance to serum complement in the complement-resistant strain Mc6. The cleavage of McaP did not cause any sensitization to erythromycin nor did NE disturb its drug action. Identifying NE as a novel but subtle anti-virulence agent together with its extracellularly not-efficient bactericidal activity against <i>M. catarrhalis</i> may facilitate the pathogen’s existence in the airways under inflammation. |
| first_indexed | 2024-03-11T05:35:26Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:35:26Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fe3cdeeaf33940b2b7222da81d216b8b2023-11-17T16:53:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01247660710.3390/ijms24076607The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase against <i>Moraxella catarrhalis</i>Justyna Roszkowiak0Siobhán McClean1Aleksandra M. Mirończuk2Daria Augustyniak3Department of Pathogen Biology and Immunology, Faculty of Biological Sciences, University of Wroclaw, 51-148 Wroclaw, PolandSchool of Biomolecular and Biomedical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, D04 V1W8 Dublin, IrelandLaboratory for Biosustainability, Institute of Environmental Biology, Wroclaw University of Environmental and Life Sciences, 51-631 Wroclaw, PolandDepartment of Pathogen Biology and Immunology, Faculty of Biological Sciences, University of Wroclaw, 51-148 Wroclaw, PolandNeutrophil elastase (NE) contributes to innate antibacterial defense at both the intracellular (phagocytosis) and extracellular (degranulation, NETosis) levels. <i>Moraxella catarrhalis</i>, a human respiratory pathogen, can exist in an inflammatory milieu which contains NE. No data are available on the action of NE against <i>M. catarrhalis</i> or on the counteraction of NE-dependent host defenses by this pathogen. Using time-kill assays we found that bacteria are able to survive and replicate in the presence of NE. Transmission electron microscopy and flow cytometry studies with NE-treated bacteria revealed that while NE admittedly destabilizes the outer membrane leaflet, it does not cause cytoplasmic membrane rupture, suggesting that the enzyme does not target components that are essential for cell integrity. Using LC-MS/MS spectroscopy we determined that NE cleaved at least three virulent surface proteins in outer membrane vesicles (OMVs) of <i>M. catarrhalis,</i> including OMP CD, McaP, and TbpA. The cleavage of OMP CD contributes to the significant decrease in resistance to serum complement in the complement-resistant strain Mc6. The cleavage of McaP did not cause any sensitization to erythromycin nor did NE disturb its drug action. Identifying NE as a novel but subtle anti-virulence agent together with its extracellularly not-efficient bactericidal activity against <i>M. catarrhalis</i> may facilitate the pathogen’s existence in the airways under inflammation.https://www.mdpi.com/1422-0067/24/7/6607neutrophil elastase<i>Moraxella catarrhalis</i>outer membrane vesicles (OMVs)outer membrane proteins (OMPs)complementanti-virulence action |
| spellingShingle | Justyna Roszkowiak Siobhán McClean Aleksandra M. Mirończuk Daria Augustyniak The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase against <i>Moraxella catarrhalis</i> International Journal of Molecular Sciences neutrophil elastase <i>Moraxella catarrhalis</i> outer membrane vesicles (OMVs) outer membrane proteins (OMPs) complement anti-virulence action |
| title | The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase against <i>Moraxella catarrhalis</i> |
| title_full | The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase against <i>Moraxella catarrhalis</i> |
| title_fullStr | The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase against <i>Moraxella catarrhalis</i> |
| title_full_unstemmed | The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase against <i>Moraxella catarrhalis</i> |
| title_short | The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase against <i>Moraxella catarrhalis</i> |
| title_sort | direct anti virulence but not bactericidal activity of human neutrophil elastase against i moraxella catarrhalis i |
| topic | neutrophil elastase <i>Moraxella catarrhalis</i> outer membrane vesicles (OMVs) outer membrane proteins (OMPs) complement anti-virulence action |
| url | https://www.mdpi.com/1422-0067/24/7/6607 |
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