The νSaα 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 νSaα 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 νSaα islands have been classified as type I...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-06-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4470592?pdf=render |
| _version_ | 1819080924966420480 |
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| author | Minh Thu Nguyen Beatrice Kraft Wenqi Yu Dogan Doruk Demircioglu Tobias Hertlein Marc Burian Mathias Schmaler Klaus Boller Isabelle Bekeredjian-Ding Knut Ohlsen Birgit Schittek Friedrich Götz |
| author_facet | Minh Thu Nguyen Beatrice Kraft Wenqi Yu Dogan Doruk Demircioglu Tobias Hertlein Marc Burian Mathias Schmaler Klaus Boller Isabelle Bekeredjian-Ding Knut Ohlsen Birgit Schittek Friedrich Götz |
| author_sort | Minh Thu Nguyen |
| collection | DOAJ |
| description | All Staphylococcus aureus genomes contain a genomic island, which is termed νSaα 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 νSaα 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 νSaα island. Since the contribution of the lpl gene cluster encoded in the νSaα 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 νSaα 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 highlights 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. |
| first_indexed | 2024-12-21T19:52:37Z |
| format | Article |
| id | doaj.art-2af8392fa1d24822a25a6656eb3c0dc7 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T19:52:37Z |
| publishDate | 2015-06-01 |
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| series | PLoS Pathogens |
| spelling | doaj.art-2af8392fa1d24822a25a6656eb3c0dc72022-12-21T18:52:10ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-06-01116e100498410.1371/journal.ppat.1004984The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells.Minh Thu NguyenBeatrice KraftWenqi YuDogan Doruk DemirciogluTobias HertleinMarc BurianMathias SchmalerKlaus BollerIsabelle Bekeredjian-DingKnut OhlsenBirgit SchittekFriedrich GötzAll Staphylococcus aureus genomes contain a genomic island, which is termed νSaα 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 νSaα 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 νSaα island. Since the contribution of the lpl gene cluster encoded in the νSaα 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 νSaα 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 highlights 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.http://europepmc.org/articles/PMC4470592?pdf=render |
| spellingShingle | Minh Thu Nguyen Beatrice Kraft Wenqi Yu Dogan Doruk Demircioglu Tobias Hertlein Marc Burian Mathias Schmaler Klaus Boller Isabelle Bekeredjian-Ding Knut Ohlsen Birgit Schittek Friedrich Götz The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells. PLoS Pathogens |
| title | The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells. |
| title_full | The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells. |
| title_fullStr | The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells. |
| title_full_unstemmed | The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells. |
| title_short | The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells. |
| title_sort | νsaα specific lipoprotein like cluster lpl of s aureus usa300 contributes to immune stimulation and invasion in human cells |
| url | http://europepmc.org/articles/PMC4470592?pdf=render |
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