The vSa\(\alpha\) Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells
All Staphylococcus aureus genomes contain a genomic island, which is termed vSa\(\alpha\) and characterized by two clusters of tandem repeat sequences, i.e. the exotoxin (set) and 'lipoprotein-like' genes (lpl). Based on their structural similarities the vSa\(\alpha\) islands have been cla...
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ftunivwuerz:oai:opus.bibliothek.uni-wuerzburg.de:15185 2023-09-05T13:11:39+02:00 The vSa\(\alpha\) Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells Nguyen, Minh Thu Kraft, Beatrice Yu, Wenqi Demicrioglu, Dogan Doruk Hertlein, Tobias Burian, Marc Schmaler, Mathias Boller, Klaus Bekeredjian-Ding, Isabelle Ohlsen, Knut Schittek, Birgit Götz, Friedrich 2015 application/pdf https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/15185 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-151856 https://doi.org/10.1371/journal.ppat.1004984 https://opus.bibliothek.uni-wuerzburg.de/files/15185/036_Minh_Thu_PLOS_PATHOGENS.PDF eng eng https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/15185 urn:nbn:de:bvb:20-opus-151856 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-151856 https://doi.org/10.1371/journal.ppat.1004984 https://opus.bibliothek.uni-wuerzburg.de/files/15185/036_Minh_Thu_PLOS_PATHOGENS.PDF https://creativecommons.org/licenses/by/4.0/deed.de info:eu-repo/semantics/openAccess ddc:610 article doc-type:article 2015 ftunivwuerz https://doi.org/10.1371/journal.ppat.1004984 2023-08-13T22:33:35Z All Staphylococcus aureus genomes contain a genomic island, which is termed vSa\(\alpha\) and characterized by two clusters of tandem repeat sequences, i.e. the exotoxin (set) and 'lipoprotein-like' genes (lpl). Based on their structural similarities the vSa\(\alpha\) islands have been classified as type I to IV. The genomes of highly pathogenic and particularly epidemic S. aureus strains (USA300, N315, Mu50, NCTC8325, Newman, COL, JH1 or JH9) belonging to the clonal complexes CC5 and CC8 bear a type I vSa\(\alpha\) island. Since the contribution of the lpl gene cluster encoded in the vSa\(\alpha\) island to virulence is unclear to date, we deleted the entire lpl gene cluster in S. aureus USA300. The results showed that the mutant was deficient in the stimulation of pro-inflammatory cytokines in human monocytes, macrophages and keratinocytes. Purified lipoprotein Lpl1 was further shown to elicit a TLR2-dependent response. Furthermore, heterologous expression of the USA300 lpl cluster in other S. aureus strains enhanced their immune stimulatory activity. Most importantly, the lpl cluster contributed to invasion of S. aureus into human keratinocytes and mouse skin and the non-invasive S. carnosus expressing the lpl gene cluster became invasive. Additionally, in a murine kidney abscess model the bacterial burden in the kidneys was higher in wild type than in mutant mice. In this infection model the lpl cluster, thus, contributes to virulence. The present report is one of the first studies addressing the role of the vSa\(\alpha\) encoded lpl gene cluster in staphylococcal virulence. The finding that the lpl gene cluster contributes to internalization into non-professional antigen presenting cells such as keratinocytes high-lights the lpl as a new cell surface component that triggers host cell invasion by S. aureus. Increased invasion in murine skin and an increased bacterial burden in a murine kidney abscess model suggest that the lpl gene cluster serves as an important virulence factor. Article in Journal/Newspaper Alpha Island Würzburg University: Online Publication Service Alpha Island ENVELOPE(-63.000,-63.000,-64.317,-64.317) PLOS Pathogens 11 6 e1004984 |
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Würzburg University: Online Publication Service |
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ddc:610 Nguyen, Minh Thu Kraft, Beatrice Yu, Wenqi Demicrioglu, Dogan Doruk Hertlein, Tobias Burian, Marc Schmaler, Mathias Boller, Klaus Bekeredjian-Ding, Isabelle Ohlsen, Knut Schittek, Birgit Götz, Friedrich The vSa\(\alpha\) Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells |
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ddc:610 |
description |
All Staphylococcus aureus genomes contain a genomic island, which is termed vSa\(\alpha\) and characterized by two clusters of tandem repeat sequences, i.e. the exotoxin (set) and 'lipoprotein-like' genes (lpl). Based on their structural similarities the vSa\(\alpha\) islands have been classified as type I to IV. The genomes of highly pathogenic and particularly epidemic S. aureus strains (USA300, N315, Mu50, NCTC8325, Newman, COL, JH1 or JH9) belonging to the clonal complexes CC5 and CC8 bear a type I vSa\(\alpha\) island. Since the contribution of the lpl gene cluster encoded in the vSa\(\alpha\) island to virulence is unclear to date, we deleted the entire lpl gene cluster in S. aureus USA300. The results showed that the mutant was deficient in the stimulation of pro-inflammatory cytokines in human monocytes, macrophages and keratinocytes. Purified lipoprotein Lpl1 was further shown to elicit a TLR2-dependent response. Furthermore, heterologous expression of the USA300 lpl cluster in other S. aureus strains enhanced their immune stimulatory activity. Most importantly, the lpl cluster contributed to invasion of S. aureus into human keratinocytes and mouse skin and the non-invasive S. carnosus expressing the lpl gene cluster became invasive. Additionally, in a murine kidney abscess model the bacterial burden in the kidneys was higher in wild type than in mutant mice. In this infection model the lpl cluster, thus, contributes to virulence. The present report is one of the first studies addressing the role of the vSa\(\alpha\) encoded lpl gene cluster in staphylococcal virulence. The finding that the lpl gene cluster contributes to internalization into non-professional antigen presenting cells such as keratinocytes high-lights the lpl as a new cell surface component that triggers host cell invasion by S. aureus. Increased invasion in murine skin and an increased bacterial burden in a murine kidney abscess model suggest that the lpl gene cluster serves as an important virulence factor. |
format |
Article in Journal/Newspaper |
author |
Nguyen, Minh Thu Kraft, Beatrice Yu, Wenqi Demicrioglu, Dogan Doruk Hertlein, Tobias Burian, Marc Schmaler, Mathias Boller, Klaus Bekeredjian-Ding, Isabelle Ohlsen, Knut Schittek, Birgit Götz, Friedrich |
author_facet |
Nguyen, Minh Thu Kraft, Beatrice Yu, Wenqi Demicrioglu, Dogan Doruk Hertlein, Tobias Burian, Marc Schmaler, Mathias Boller, Klaus Bekeredjian-Ding, Isabelle Ohlsen, Knut Schittek, Birgit Götz, Friedrich |
author_sort |
Nguyen, Minh Thu |
title |
The vSa\(\alpha\) Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells |
title_short |
The vSa\(\alpha\) Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells |
title_full |
The vSa\(\alpha\) Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells |
title_fullStr |
The vSa\(\alpha\) Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells |
title_full_unstemmed |
The vSa\(\alpha\) Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells |
title_sort |
vsa\(\alpha\) specific lipoprotein like cluster (lpl) of s. aureus usa300 contributes to immune stimulation and invasion in human cells |
publishDate |
2015 |
url |
https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/15185 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-151856 https://doi.org/10.1371/journal.ppat.1004984 https://opus.bibliothek.uni-wuerzburg.de/files/15185/036_Minh_Thu_PLOS_PATHOGENS.PDF |
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ENVELOPE(-63.000,-63.000,-64.317,-64.317) |
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Alpha Island |
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Alpha Island |
genre |
Alpha Island |
genre_facet |
Alpha Island |
op_relation |
https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/15185 urn:nbn:de:bvb:20-opus-151856 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-151856 https://doi.org/10.1371/journal.ppat.1004984 https://opus.bibliothek.uni-wuerzburg.de/files/15185/036_Minh_Thu_PLOS_PATHOGENS.PDF |
op_rights |
https://creativecommons.org/licenses/by/4.0/deed.de info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1371/journal.ppat.1004984 |
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PLOS Pathogens |
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e1004984 |
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