Fraunhofer Institute for Interfacial Eng & Biotechnology IGB

Staphylococcus aureus is a major opportunistic pathogen in humans and animals. More than 90% of human nasal S. aureus isolates carry Sa3int-phages that integrate into the bacterial hlb gene coding for a sphingomyelinase. Sa3int-phages encode highly human-specific virulence factors that enable S. aureus to adapt to the human host. Thus, balancing mechanisms are necessary for the phage-bacteria coexistence. However, the factors that coordinate these interactions have yet to be discovered. Here, we elucidate the impact of the DNA-binding protein SarA on the life cycle of two prototypic S. aureus phages, Sa3int Φ13 and Sa5int Φ11. SarA promotes the propagation of both phages, albeit via different mechanisms. SarA promotes Φ11 propagation by repressing the glycosyltransferase TarM, which affects the glycosylation pattern of the phage receptor, wall teichoic acid, thereby improving phage adsorption. SarA also dampens the DNA damage response as indicated by the downregulation of the ci and mor phage promoters and the umuC SOS target gene, as well as inhibition of Φ11 inducibility. For Φ13, however, SarA promotes phage replication rather than inhibiting phage induction. The replication-deficient phage Φ13K- rep was SarA-insensitive, and phage gene expression was unaltered in the sarA mutant. These results highlight SarA as a regulator of temperate phage propagation and support its role as a DNA structural protein that promotes phage replication.

The dynamic gain and loss of temperate phages is crucial for bacteria to adapt to specific niches. In Staphylococcus aureus Sa3int, phages are highly prevalent in human strains but are missing in most animal strains. The mechanisms that balance phage-bacteria coexistence are only partially understood. We demonstrate that the DNA-binding protein SarA is a key regulator of the phage life cycle. SarA protects bacteria from phage induction in response to DNA damage, yet it can also promote phage propagation by altering the phage receptor or interfering with phage replication. SarA likely functions not only as a transcriptional factor, but also as a bacterial chromosome structural component that controls the phage life cycle at different levels.

Herein, the synthesis and characterization of highly sulfonated poly(arylene thioethers) for application as polymer electrolyte membranes in water electrolysis are reported. In a first step, poly(arylene thioethers) were obtained by using mild reaction conditions of a polycondensation reaction between 4,4'-thiobisbenzenethiol and decafluorobiphenyl. In a second step, the resulting poly(arylene thioethers) were sulfonated by a fluorothiol displacement click reaction of the fluorinated monomers by sodium 3-mercapto-1-propanesulfonate. Thus, highly sulfonated polymers were obtained, resulting in water-soluble ionomers. Stable polymer electrolyte membranes with enhanced thermal and chemical stability were attained by blending ionomers with a poly(benzimidazole) derivative (PBI-OO). The resulting proton-exchange membranes (PEMs) based on the new sulfonated ionomer PBI-OO blends showed about 40% higher proton conductivity than Nafion at 90 °C. The proton-conducting membranes with the highest conductivity and best film-forming properties were applied for water electrolysis. Combined with optimized water oxidation and reduction catalysts, the selected tetra-sulfonated polymer-based PEM reached 1.784 V at 1 A cm^-2 in the electrolysis of pure water.

Psoriasis is a multifactorial systemic autoinflammatory disease that is characterized by complex signaling between keratinocytes and immune cells. The trigger factors for the cutaneous manifestation of the disease are divers but have in common that they induce an activation of the Toll-like receptor (TLR) signaling pathways. This is best described for the activation of TLR7/8/9 in dendritic cells. In this study, we investigated the role of TLR2 and TLR3 activation in keratinocytes for the expression of psoriatic hallmarks in the skin. We set up 3D epidermis models using wild type keratinocytes and TLR2 knockout and TLR3 knockout (KO) keratinocytes derived from the wild type keratinocytes and treated them with TLR agonists. Immunohistochemical, western blot, and multiplex analysis showed that the TLR activation induced the expression of psoriasis associated markers like S100A7, p-STAT3, CXCL-1, IL-8, IL-1α, S100A9, and IL-23 in the wild type but not in the TLR KO epidermis models. Thus, TLR2 and TLR3 activation in keratinocytes individually contributes significantly to inducing the release of cytokines and other immune modulators characteristic for a psoriasis like inflammation in 3D epidermis models.