No abstract

The pathogenicity of group A Streptococcus (GAS) is mediated by direct bacterial invasivity and toxin-associated damage. Among the extracellular products, the exotoxin streptolysin O (SLO) is produced by almost all GAS strains. SLO is a pore forming toxin (PFT) hemolitically active and extremely toxic in vivo. Recent evidence suggests that human serum albumin (HSA), the most abundant protein in plasma, is a player in the innate immunity “orchestra.” We previously demonstrated that HSA acts as a physiological buffer, partially neutralizing Clostridioides difficile toxins that reach the bloodstream after being produced in the colon. Here, we report the in vitro and ex vivo capability of HSA to neutralize the cytotoxic and hemolytic effects of SLO. HSA binds SLO with high affinity at a non-conventional site located in domain II, which was previously reported to interact also with C. difficile toxins. HSA:SLO recognition protects HEp-2 and A549 cells from cytotoxic effects and cell membrane permeabilization induced by SLO. Moreover, HSA inhibits the SLO-dependent hemolytic effect in red blood cells isolated from healthy human donors. The recognition of SLO by HSA may have a significant protective role in human serum and sustains the emerging hypothesis that HSA is an important constituent of the innate immunity system.

No abstract

Serum albumin (SA) is the most abundant protein in plasma and represents the main carrier of endogenous and exogenous compounds. Several evidence supports the notion that SA binds single and double‐stranded deoxynucleotides and ribonucleotides at two sites, with values of the dissociation equilibrium constant (i.e., Kd) ranging from micromolar to nanomolar values. This can be relevant from a physiological and pathological point of view, as in human plasma circulates cell‐free nucleic acids (cfNAs), released by different tissues via apoptosis, necrosis, and secretions, circulates as single and double‐stranded NAs. Albeit SA shows low hydrolytic reactivity toward DNA and RNA, the high plasma concentration of this protein and the occurrence of several SA receptors may be pivotal for sequestering and hydrolyzing cfNAs. Therefore, pathological conditions like cancer, characterized by altered levels of human SA or by altered SA post‐translational modifications, may influence cfNAs distribution and metabolism. Besides, the stability, solubility, biocompatibility, and low immunogenicity make SA a golden share for biotechnological applications related to the delivery of therapeutic NAs (TNAs). Indeed, pre‐clinical studies report the therapeutic potential of SA:TNAs complexes in precision cancer therapy. Here, the molecular and biotechnological implications of SA:NAs interaction are discussed, highlighting new perspectives on SA plasmatic functions.

Mechanical robustness, biocompatibility, and antibacterial performances are key features for materials suitable to be used in tissue engineering applications. In this work, we investigated the link existing between structural and functional properties of TiCu(Ag) thin films deposited by physical vapor deposition magnetron sputtering on Si substrates. The thin films were characterized by X-ray diffraction (XRD), nanoindentation, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). The TiCu(Ag) thin films showed complete amorphous structure and improved mechanical properties in comparison with pure Ti films. However, for contents in excess of 20% Ag, we observed the appearance of nanometric Ag crystallite. The TiCu(Ag) thin films displayed excellent biocompatibility properties, allowing adhesion and proliferation of the human fibroblasts MRC-5 cell line. Moreover, all the investigated TiCu(Ag) alloy display bactericidal properties, preventing the growth of both Pseudomonas aeruginosa and Staphylococcus aureus. Results obtained from biological tests have been correlated to the surface structure and microstructure of films. The excellent biocompatibility and bactericidal properties of these multifunctional thin films opens to their use in tissue engineering applications.