Biology subjects

Weidenmaier, C.

Publications and source records attributed to Weidenmaier, C..

2 recordsLinked to original sources

bioRxiv2018

The biogenesis of extracellular vesicles from Staphylococcus aureus and their application as a novel vaccine platform

Gram-positive bacteria secrete extracellular vesicles (EVs) that package diverse bacterial antigens and play key roles in bacterial pathogenesis. However, the mechanisms underlying EV production in Gram-positive bacteria are poorly understood. We purified and characterized EVs from a community-associated methicillin-resistant Staphylococcus aureus isolate (USA300) and investigated mechanisms underlying EV production. Native EVs contained 165 proteins, including cytosolic, surface, and secreted proteins, autolysins, and numerous cytolysins. Staphylococcal alpha-type phenol-soluble modulins (surfactant-like peptides) promoted EV biogenesis, presumably by acting at the cytoplasmic membrane, whereas peptidoglycan crosslinking and autolysin activity were found to increase EV production by altering the permeability of the staphylococcal cell wall. To address the immunogenicity of EVs, we created engineered EVs (eng-EVs) by expressing detoxified proteins HlaH35L and LukE in EVs generated from a nontoxic S. aureus {Delta}agr{Delta}spa mutant. Eng-EVs exhibited no cytotoxicity in vitro, and mice immunized with the eng-EVs produced toxin-neutralizing antibodies and showed reduced lethality in a mouse sepsis model. Our study reveals novel mechanisms underlying S. aureus EV production and highlights the usefulness of EVs as a novel S. aureus vaccine platform.

microbiology↗

bioRxiv2017

Wall teichoic acid is a pathogen-associated molecular pattern of Staphylococcus aureus that is recognized by langerin (CD207) on skin Langerhans cells

Staphylococcus aureus is a major cause of skin and soft tissue infections and aggravator of the inflammatory skin disease atopic dermatitis (AD). Epicutaneous exposure to S. aureus induces Th17 responses through skin Langerhans cells (LCs), which paradoxically contribute to host defense but also to AD pathogenesis. The underlying molecular mechanisms of the association between S. aureus and skin inflammation are poorly understood. Here, we demonstrate that human LCs directly interact with S. aureus through the pattern-recognition receptor langerin (CD207). Human, but not mouse, langerin interacts with S. aureus through the conserved {beta}-N-acetylglucosamine (GlcNAc) modifications on wall teichoic acid (WTA), thereby discriminating S. aureus from other staphylococcal species. Importantly, the specific S. aureus WTA glycoprofile strongly influences the level of Th1-and Th17-polarizing cytokines that are produced by in vitro generated LCs. Finally, in a murine epicutaneous infection model, S. aureus induced a more pronounced influx of inflammatory cells and pro-inflammatory cytokine transcripts in skin of human langerin transgenic mice compared to wild-type mice. Our findings provide molecular insight into the unique pro-inflammatory capacities of S. aureus in relation to inflammatory skin disease.

microbiology↗