ABSTRACT
Poly(N-vinyl pyrrolidone) (PVP)-based hydrogels with titania nanoparticles (TN) were synthesized by the sol-gel method for the first time and were characterized in different states (native, freeze-dried, air-dried to constant weight and ground to powder, or swollen to constant weight in H2O or D2O) by various methods such as wide-angle and small-angle X-ray and neutron scattering, neutron spin-echo (NSE) spectroscopy, and scanning electron microscopy. The static (static polymer-polymer correlation length (mesh size), associates of cross-links and PVP microchains) and dynamic (polymer chain relaxation rate, hydrodynamic polymer-polymer correlation length) structural elements were determined. The incorporation of titania nanoparticles into PVP hydrogel slightly increases the size of structural inhomogeneities (an increase in the static and dynamic polymer-polymer correlation length, the formation of associates of cross-links and PVP chains). Titania nanoparticles have an impact on the microstructure of the composite hydrogel and form associates with sizes from 0.5 to 2 µm attached to PVP hydrogel pore walls. The PVP and TN/PVP hydrogels show a high degree of water swelling. Moreover, the presence of titania nanoparticles in TN/PVP increases the number of water adsorption cycles compared to PVP hydrogel. The high swelling degree, bacteria-resistant and antimicrobial properties against Staphylococcus aureus allow considering NT/PVP hydrogels for medical applications as wound coatings.
ABSTRACT
Staphylococcus aureus can cause devastating and life-threatening infections. With the increase in multidrug resistant strains, novel therapies are needed. Limited success with active and passive immunization strategies have been attributed to S. aureus immune evasion. Here, we report on a monoclonal antibody, 514G3, that circumvents a key S. aureus evasion mechanism by targeting the cell wall moiety Protein A (SpA). SpA tightly binds most subclasses of immunoglobulins via their Fc region, neutralizing effector function. The organism can thus shield itself with a protective coat of serum antibodies and render humoral immunity ineffective. The present antibody reactivity was derived from an individual with natural anti-SpA antibody titers. The monoclonal antibody is of an IgG3 subclass, which differs critically from other immunoglobulin subclasses since its Fc is not bound by SpA. Moreover, it targets a unique epitope on SpA that allows it to bind in the presence of serum antibodies. Consequently, the antibody opsonizes S. aureus and maintains effector function to enable natural immune mediated clearance. The data presented here provide evidence that 514G3 antibody is able to successfully rescue mice from S. aureus mediated bacteremia.
