Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl <i>cis/trans</i> Isomerase Enzymes in <i>Staphylococcus aureus</i>
Peptidyl-prolyl <i>cis/trans</i> isomerases (PPIases) are enzymes that catalyze the <i>cis</i>-to-<i>trans</i> isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in <i>S...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-06-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/11/6/343 |
| _version_ | 1798039732169474048 |
|---|---|
| author | Rebecca A. Keogh Rachel L. Zapf Emily Trzeciak Gillian G. Null Richard E. Wiemels Ronan K. Carroll |
| author_facet | Rebecca A. Keogh Rachel L. Zapf Emily Trzeciak Gillian G. Null Richard E. Wiemels Ronan K. Carroll |
| author_sort | Rebecca A. Keogh |
| collection | DOAJ |
| description | Peptidyl-prolyl <i>cis/trans</i> isomerases (PPIases) are enzymes that catalyze the <i>cis</i>-to-<i>trans</i> isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in <i>Staphylococcus aureus</i> (PpiB and PrsA) that are involved in the regulation of virulence determinants and have shown that PpiB contributes to <i>S. aureus</i> virulence in a murine abscess model of infection. Here, we further examine the role of these PPIases in <i>S. aureus</i> virulence and, in particular, their regulation of hemolytic toxins. Using murine abscess and systemic models of infection, we show that a <i>ppiB</i> mutant in a USA300 background is attenuated for virulence but that a <i>prsA</i> mutant is not. Deletion of the <i>ppiB</i> gene leads to decreased bacterial survival in macrophages and nasal epithelial cells, while there is no significant difference when <i>prsA</i> is deleted. Analysis of culture supernatants reveals that a <i>ppiB</i> mutant strain has reduced levels of the phenol-soluble modulins and that both <i>ppiB</i> and <i>prsA</i> mutants have reduced alpha-toxin activity. Finally, we perform immunoprecipitation to identify cellular targets of PpiB and PrsA. Results suggest a novel role for PpiB in <i>S. aureus</i> protein secretion. Collectively, our results demonstrate that PpiB and PrsA influence <i>S. aureus</i> toxins via distinct mechanisms, and that PpiB but not PrsA contributes to disease. |
| first_indexed | 2024-04-11T21:57:48Z |
| format | Article |
| id | doaj.art-ab066ce664554c9e9eeda9c31227cc9e |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T21:57:48Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-ab066ce664554c9e9eeda9c31227cc9e2022-12-22T04:01:03ZengMDPI AGToxins2072-66512019-06-0111634310.3390/toxins11060343toxins11060343Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl <i>cis/trans</i> Isomerase Enzymes in <i>Staphylococcus aureus</i>Rebecca A. Keogh0Rachel L. Zapf1Emily Trzeciak2Gillian G. Null3Richard E. Wiemels4Ronan K. Carroll5Department of Biological Sciences, Ohio University, Athens, OH 45701, USADepartment of Biological Sciences, Ohio University, Athens, OH 45701, USADepartment of Biological Sciences, Ohio University, Athens, OH 45701, USADepartment of Biological Sciences, Ohio University, Athens, OH 45701, USADepartment of Biological Sciences, Ohio University, Athens, OH 45701, USADepartment of Biological Sciences, Ohio University, Athens, OH 45701, USAPeptidyl-prolyl <i>cis/trans</i> isomerases (PPIases) are enzymes that catalyze the <i>cis</i>-to-<i>trans</i> isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in <i>Staphylococcus aureus</i> (PpiB and PrsA) that are involved in the regulation of virulence determinants and have shown that PpiB contributes to <i>S. aureus</i> virulence in a murine abscess model of infection. Here, we further examine the role of these PPIases in <i>S. aureus</i> virulence and, in particular, their regulation of hemolytic toxins. Using murine abscess and systemic models of infection, we show that a <i>ppiB</i> mutant in a USA300 background is attenuated for virulence but that a <i>prsA</i> mutant is not. Deletion of the <i>ppiB</i> gene leads to decreased bacterial survival in macrophages and nasal epithelial cells, while there is no significant difference when <i>prsA</i> is deleted. Analysis of culture supernatants reveals that a <i>ppiB</i> mutant strain has reduced levels of the phenol-soluble modulins and that both <i>ppiB</i> and <i>prsA</i> mutants have reduced alpha-toxin activity. Finally, we perform immunoprecipitation to identify cellular targets of PpiB and PrsA. Results suggest a novel role for PpiB in <i>S. aureus</i> protein secretion. Collectively, our results demonstrate that PpiB and PrsA influence <i>S. aureus</i> toxins via distinct mechanisms, and that PpiB but not PrsA contributes to disease.https://www.mdpi.com/2072-6651/11/6/343PPIase<i>S. aureus</i>toxinsPpiBPrsAalpha-toxinPSMs |
| spellingShingle | Rebecca A. Keogh Rachel L. Zapf Emily Trzeciak Gillian G. Null Richard E. Wiemels Ronan K. Carroll Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl <i>cis/trans</i> Isomerase Enzymes in <i>Staphylococcus aureus</i> Toxins PPIase <i>S. aureus</i> toxins PpiB PrsA alpha-toxin PSMs |
| title | Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl <i>cis/trans</i> Isomerase Enzymes in <i>Staphylococcus aureus</i> |
| title_full | Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl <i>cis/trans</i> Isomerase Enzymes in <i>Staphylococcus aureus</i> |
| title_fullStr | Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl <i>cis/trans</i> Isomerase Enzymes in <i>Staphylococcus aureus</i> |
| title_full_unstemmed | Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl <i>cis/trans</i> Isomerase Enzymes in <i>Staphylococcus aureus</i> |
| title_short | Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl <i>cis/trans</i> Isomerase Enzymes in <i>Staphylococcus aureus</i> |
| title_sort | novel regulation of alpha toxin and the phenol soluble modulins by peptidyl prolyl i cis trans i isomerase enzymes in i staphylococcus aureus i |
| topic | PPIase <i>S. aureus</i> toxins PpiB PrsA alpha-toxin PSMs |
| url | https://www.mdpi.com/2072-6651/11/6/343 |
| work_keys_str_mv | AT rebeccaakeogh novelregulationofalphatoxinandthephenolsolublemodulinsbypeptidylprolylicistransiisomeraseenzymesinistaphylococcusaureusi AT rachellzapf novelregulationofalphatoxinandthephenolsolublemodulinsbypeptidylprolylicistransiisomeraseenzymesinistaphylococcusaureusi AT emilytrzeciak novelregulationofalphatoxinandthephenolsolublemodulinsbypeptidylprolylicistransiisomeraseenzymesinistaphylococcusaureusi AT gilliangnull novelregulationofalphatoxinandthephenolsolublemodulinsbypeptidylprolylicistransiisomeraseenzymesinistaphylococcusaureusi AT richardewiemels novelregulationofalphatoxinandthephenolsolublemodulinsbypeptidylprolylicistransiisomeraseenzymesinistaphylococcusaureusi AT ronankcarroll novelregulationofalphatoxinandthephenolsolublemodulinsbypeptidylprolylicistransiisomeraseenzymesinistaphylococcusaureusi |