Abstract
The Sec pathway plays a prominent role in protein export and membrane insertion, including the secretion of major bacterial virulence determinants. The accessory Sec constituent SecDF has been proposed to contribute to protein export. Deletion of Staphylococcus aureus secDF has previously been shown to reduce resistance, to alter cell separation, and to change the expression of certain virulence factors. To analyse the impact of the secDF deletion in S. aureus on protein secretion, a quantitative secretome analysis was performed. Numerous Sec signal containing proteins involved in virulence were found to be decreased in the supernatant of the secDF mutant. However, two Sec-dependent hydrolases were increased in comparison to the wild type, suggesting additional indirect, regulatory effects to occur upon deletion of secDF. Adhesion, invasion, and cytotoxicity of the secDF mutant were reduced in human umbilical vein endothelial cells. Virulence was significantly reduced using a Galleria mellonella insect model. Altogether, SecDF is a promising therapeutic target for controlling S. aureus infections.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacterial Proteins / genetics*
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Bacterial Proteins / metabolism
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Gene Expression Regulation, Bacterial*
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Human Umbilical Vein Endothelial Cells
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Humans
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Membrane Proteins / deficiency
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Membrane Transport Proteins / deficiency
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Membrane Transport Proteins / genetics*
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Membrane Transport Proteins / metabolism
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Moths / microbiology
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Protein Transport
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Staphylococcus aureus / genetics*
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Staphylococcus aureus / metabolism
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Staphylococcus aureus / pathogenicity*
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Transcriptome*
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Virulence
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Virulence Factors / genetics*
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Virulence Factors / metabolism
Substances
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Bacterial Proteins
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Membrane Proteins
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Membrane Transport Proteins
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Virulence Factors
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secD protein, Bacteria
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secF protein, Bacteria
Grants and funding
This study was supported by the Gottfried und Julia Bangerter-Rhyner-Stiftung to CQ and by grants of the Foundation for Research at the Medical Faculty, University of Zurich and Matching Funds of the Clinical Trials Center, University Hospital Zurich to KS. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 241446 (project ANTIRESDEV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.