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Staphylococcus aureus Exploits a Non-ribosomal Cyclic Dipeptide to Modulate Survival within Epithelial Cells and Phagocytes
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نویسنده
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blättner s. ,das s. ,paprotka k. ,eilers u. ,krischke m. ,kretschmer d. ,remmele c.w. ,dittrich m. ,müller t. ,schuelein-voelk c. ,hertlein t. ,mueller m.j. ,huettel b. ,reinhardt r. ,ohlsen k. ,rudel t. ,fraunholz m.j.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 9
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چکیده
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Community-acquired (ca) staphylococcus aureus cause various diseases even in healthy individuals. enhanced virulence of ca-strains is partly attributed to increased production of toxins such as phenol-soluble modulins (psm). the pathogen is internalized efficiently by mammalian host cells and intracellular s. aureus has recently been shown to contribute to disease. upon internalization,cytotoxic s. aureus strains can disrupt phagosomal membranes and kill host cells in a psm-dependent manner. however,psm are not sufficient for these processes. here we screened for factors required for intracellular s. aureus virulence. we infected escape reporter host cells with strains from an established transposon mutant library and detected phagosomal escape rates using automated microscopy. we thereby,among other factors,identified a non-ribosomal peptide synthetase (nrps) to be required for efficient phagosomal escape and intracellular survival of s. aureus as well as induction of host cell death. by genetic complementation as well as supplementation with the synthetic nrps product,the cyclic dipeptide phevalin,wild-type phenotypes were restored. we further demonstrate that the nrps is contributing to virulence in a mouse pneumonia model. together,our data illustrate a hitherto unrecognized function of the s. aureus nrps and its dipeptide product during s. aureus infection. © 2016 blättner et al.
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آدرس
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biocenter,chair of microbiology,university of würzburg,würzburg, Germany, biocenter,chair of microbiology,university of würzburg,würzburg, Germany, biocenter,chair of microbiology,university of würzburg,würzburg, Germany, core unit functional genomics,university of würzburg,würzburg, Germany, biocenter,chair of pharmaceutical biology,university of würzburg,würzburg, Germany, department of infection biology,interfaculty institute for microbiology and infection medicine tübingen (imit),university tübingen,tübingen, Germany, biocenter,chair of bioinformatics,university of würzburg,würzburg, Germany, biocenter,chair of bioinformatics,university of würzburg,würzburg,germany,institute of human genetics,university of würzburg,würzburg, Germany, biocenter,chair of bioinformatics,university of würzburg,würzburg, Germany, core unit functional genomics,university of würzburg,würzburg, Germany, institute for molecular infection biology,university of würzburg,würzburg, Germany, biocenter,chair of pharmaceutical biology,university of würzburg,würzburg, Germany, max planck genome centre,cologne, Germany, max planck genome centre,cologne, Germany, institute for molecular infection biology,university of würzburg,würzburg, Germany, biocenter,chair of microbiology,university of würzburg,würzburg, Germany, biocenter,chair of microbiology,university of würzburg,würzburg, Germany
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Authors
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