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Open AccessArticle

Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl cis/trans Isomerase Enzymes in Staphylococcus aureus

1
Department of Biological Sciences, Ohio University, Athens, OH 45701, USA
2
The Infectious and Tropical Disease Institute, Ohio University, Athens, OH 45701, USA
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(6), 343; https://doi.org/10.3390/toxins11060343
Received: 30 April 2019 / Revised: 10 June 2019 / Accepted: 12 June 2019 / Published: 16 June 2019
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
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Abstract

Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that catalyze the cis-to-trans isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in Staphylococcus aureus (PpiB and PrsA) that are involved in the regulation of virulence determinants and have shown that PpiB contributes to S. aureus virulence in a murine abscess model of infection. Here, we further examine the role of these PPIases in S. aureus virulence and, in particular, their regulation of hemolytic toxins. Using murine abscess and systemic models of infection, we show that a ppiB mutant in a USA300 background is attenuated for virulence but that a prsA mutant is not. Deletion of the ppiB gene leads to decreased bacterial survival in macrophages and nasal epithelial cells, while there is no significant difference when prsA is deleted. Analysis of culture supernatants reveals that a ppiB mutant strain has reduced levels of the phenol-soluble modulins and that both ppiB and prsA 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 S. aureus protein secretion. Collectively, our results demonstrate that PpiB and PrsA influence S. aureus toxins via distinct mechanisms, and that PpiB but not PrsA contributes to disease. View Full-Text
Keywords: PPIase; S. aureus; toxins; PpiB; PrsA; alpha-toxin; PSMs PPIase; S. aureus; toxins; PpiB; PrsA; alpha-toxin; PSMs
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Keogh, R.A.; Zapf, R.L.; Trzeciak, E.; Null, G.G.; Wiemels, R.E.; Carroll, R.K. Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl cis/trans Isomerase Enzymes in Staphylococcus aureus. Toxins 2019, 11, 343.

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