Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms [version 1; peer review: 2 approved]
Background: Staphylococcus aureus causes an array of diseases in both humans and livestock. Pathogenesis is mediated by a plethora of proteins secreted by S. aureus, many of which remain incompletely characterised. For example, S. aureus abundantly secretes two isoforms of the enzyme lipase into the...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wellcome
2020-12-01
|
| Series: | Wellcome Open Research |
| Online Access: | https://wellcomeopenresearch.org/articles/5-286/v1 |
| _version_ | 1818662465265729536 |
|---|---|
| author | Fiona Sargison Joana Alves Amy Pickering J Ross Fitzgerald |
| author_facet | Fiona Sargison Joana Alves Amy Pickering J Ross Fitzgerald |
| author_sort | Fiona Sargison |
| collection | DOAJ |
| description | Background: Staphylococcus aureus causes an array of diseases in both humans and livestock. Pathogenesis is mediated by a plethora of proteins secreted by S. aureus, many of which remain incompletely characterised. For example, S. aureus abundantly secretes two isoforms of the enzyme lipase into the extracellular milieu, where they scavenge upon polymeric triglycerides. It has previously been suggested that lipases may interfere with the function of innate immune cells, such as macrophages and neutrophils, but the impact of lipases on phagocytic killing mechanisms remains unknown. Methods: We employed the epidemic S. aureus clone USA300 strain LAC and its lipase deficient isogenic mutant, along with recombinant lipase proteins, in in vitro experimental infection assays. To determine if lipases can inhibit innate immune killing mechanisms, the bactericidal activity of whole blood, human neutrophils, and macrophages was analysed. In addition, gentamycin protection assays were carried out to examine the influence of lipases on S. aureus innate immune cell escape. Results: There were no differences in the survival of S. aureus USA300 LAC wild type and its lipase-deficient isogenic mutant after incubation with human whole blood or neutrophils. Furthermore, there was no detectable lipase-dependent effect on phagocytosis, intracellular survival, or escape from both human primary and immortalised cell line macrophages, even upon supplementation with exogenous recombinant lipases. Conclusions: S. aureus lipases do not inhibit bacterial killing mechanisms of human macrophages, neutrophils, or whole blood. These findings broaden our understanding of the interaction of S. aureus with the innate immune system. |
| first_indexed | 2024-12-17T05:01:23Z |
| format | Article |
| id | doaj.art-ce4f6497af8443f5a0dbbfad21a15832 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-12-17T05:01:23Z |
| publishDate | 2020-12-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-ce4f6497af8443f5a0dbbfad21a158322022-12-21T22:02:33ZengWellcomeWellcome Open Research2398-502X2020-12-01510.12688/wellcomeopenres.16194.117782Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms [version 1; peer review: 2 approved]Fiona Sargison0Joana Alves1Amy Pickering2J Ross Fitzgerald3The Roslin Institute, Edinburgh, UKThe Roslin Institute, Edinburgh, UKThe Roslin Institute, Edinburgh, UKThe Roslin Institute, Edinburgh, UKBackground: Staphylococcus aureus causes an array of diseases in both humans and livestock. Pathogenesis is mediated by a plethora of proteins secreted by S. aureus, many of which remain incompletely characterised. For example, S. aureus abundantly secretes two isoforms of the enzyme lipase into the extracellular milieu, where they scavenge upon polymeric triglycerides. It has previously been suggested that lipases may interfere with the function of innate immune cells, such as macrophages and neutrophils, but the impact of lipases on phagocytic killing mechanisms remains unknown. Methods: We employed the epidemic S. aureus clone USA300 strain LAC and its lipase deficient isogenic mutant, along with recombinant lipase proteins, in in vitro experimental infection assays. To determine if lipases can inhibit innate immune killing mechanisms, the bactericidal activity of whole blood, human neutrophils, and macrophages was analysed. In addition, gentamycin protection assays were carried out to examine the influence of lipases on S. aureus innate immune cell escape. Results: There were no differences in the survival of S. aureus USA300 LAC wild type and its lipase-deficient isogenic mutant after incubation with human whole blood or neutrophils. Furthermore, there was no detectable lipase-dependent effect on phagocytosis, intracellular survival, or escape from both human primary and immortalised cell line macrophages, even upon supplementation with exogenous recombinant lipases. Conclusions: S. aureus lipases do not inhibit bacterial killing mechanisms of human macrophages, neutrophils, or whole blood. These findings broaden our understanding of the interaction of S. aureus with the innate immune system.https://wellcomeopenresearch.org/articles/5-286/v1 |
| spellingShingle | Fiona Sargison Joana Alves Amy Pickering J Ross Fitzgerald Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms [version 1; peer review: 2 approved] Wellcome Open Research |
| title | Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms [version 1; peer review: 2 approved] |
| title_full | Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms [version 1; peer review: 2 approved] |
| title_fullStr | Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms [version 1; peer review: 2 approved] |
| title_full_unstemmed | Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms [version 1; peer review: 2 approved] |
| title_short | Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms [version 1; peer review: 2 approved] |
| title_sort | staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms version 1 peer review 2 approved |
| url | https://wellcomeopenresearch.org/articles/5-286/v1 |
| work_keys_str_mv | AT fionasargison staphylococcusaureussecretedlipasesdonotinhibitinnateimmunekillingmechanismsversion1peerreview2approved AT joanaalves staphylococcusaureussecretedlipasesdonotinhibitinnateimmunekillingmechanismsversion1peerreview2approved AT amypickering staphylococcusaureussecretedlipasesdonotinhibitinnateimmunekillingmechanismsversion1peerreview2approved AT jrossfitzgerald staphylococcusaureussecretedlipasesdonotinhibitinnateimmunekillingmechanismsversion1peerreview2approved |