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Candida albicansbelongs to our commensal mucosal flora and in immune-competent individuals in the absence of epithelial damage, this fungus is well tolerated and controlled by our immune defense. However, C. albicansis an opportunistic microorganism that can cause different forms of infections, ranging from superficial to life-threatening systemic infections. C. albicansis polymorphic and switches between different phenotypes (e.g. from yeast form to hyphal form). C. albicanshyphae are invasive and can grow into tissues to eventually reach circulation. During fungal infections, neutrophils in particular play a critical role for the defense, but how neutrophils are directed toward the invasive forms of fungi is less well understood. We set out to investigate possible neutrophil chemoattractants released by C. albicansinto culture supernatants. We found that cell-free culture supernatants from the hyphal form of C. albicansinduced both neutrophil chemotaxis and concomitant intracellular calcium transients. Size separation and hydrophobic sorting of supernatants indicated small hydrophilic factors as responsible for the activity. Further analysis showed that the culture supernatants contained high levels of short-chain fatty acids with higher levels from hyphae as compared to yeast. Short-chain fatty acids are known neutrophil chemoattractants acting via the neutrophil free fatty acid receptor 2. In line with this, the calcium signaling in neutrophils induced by hyphae culture supernatants was blocked by a free fatty acid receptor 2 antagonist and potently increased in the presence of a positive allosteric modulator. Our data imply that short-chain fatty acids may act as a recruitment signal whereby neutrophils can detect C. albicanshyphae.During hyphal growth, Candida albicansrelease high levels of short-chain fatty acids which can function as end-point chemoattractants directing neutrophils toward invasive growth forms of C. albicans.

The reaction of 2,5-bis[N,N′-bis(2-pyridyl-aminomethyl)aminomethyl]-p-hydroquinone (H2bpymah) with VO2+salts in acetonitrile or water at a low pH (2.2–3.5) results in the isolation of [{VIV(O)(Cl)}2(μ-bpymah)], the p-semiquinonate complex [{VIV(O)(Cl)}2(μ-bpymas)](OH), the cyclic mixed-valent hexanuclear compound [{VV(O)(μ-O)VIV(O)}(μ-bpymah)]3, and [(VVO2)2(μ-bpymah)]. [{VIV(O)(Cl)}2(μ-bpymas)](OH) is an intermediate of the radical-mediated oxidation of [{VIV(O)(Cl)}2(μ-bpymah)] from O2. At lower pH values (2.2), a reversible intramolecular electron transfer from the metal to the ligand of [{VIV(O)(Cl)}2(μ-bpymas)](OH) is induced with the concurrent substitution of chlorine atoms by the oxygen-bridging atoms, resulting in the formation of [{VV(O)(μ-O)VIV(O)}(μ-bpymah)]3. The metal complexes were fully characterized by X-ray crystallography, infrared (IR) spectroscopy, and magnetic measurements in the solid state, as well as by conductivity measurements, UV–vis spectroscopy, and electrochemical measurements in solution. The oxidation states of the metal ions and ligands were determined by the crystallographic data. The [{VIV(O)(Cl)}2(μ-bpymah)]–[{VIV(O)(Cl)}2(μ-bpymas)](OH) redox process is electrochemically reversible. The VIVion in the semiquinonate compound exhibits a surprisingly low oxophilicity, resulting in the stabilization of OH–counterions at acidic pH values. An investigation of the mechanism of this reaction reveals that these complexes induce the reduction of O2to H2O2, mimicking the activity of enzymes incorporating two redox-active centers (metal–organic) in the active site.