Group B Streptococcus (GBS) emerged as a leading cause of invasive infectious disease in neonates in the 1970s, but has recently been identified as an escalating public health threat in non-pregnant adults, particularly those of advanced aged or underlying medical conditions. GBS infection can rapidly develop into life-threatening disease despite prompt administration of effective antibiotics and initiation of state-of-the-art intensive care protocols and technologies due to deleterious bacterial virulence factors, such as the GBS pore-forming toxin β-hemolysin/cytolysin (β-H/C). β-H/C is known to have noxious effects on a wide range of host cells and tissues, including lung epithelial cell injury, blood brain barrier weakening, and immune cell apoptosis. Neonatal and adult survivors of GBS infection are at a high risk for substantial long-term health issues and neurologic disabilities due to perturbations in organ systems caused by bacterial- and host- mediated inflammatory stressors. Previously engineered anti-virulence inhibitors, such as monoclonal antibodies and small molecular inhibitors, generally require customized design for each different pathogenic toxin and do not target deleterious host pro-inflammatory responses that may cause organ injury, septic shock, or death. By simply wrapping donor red blood cells (RBCs) around polymeric cores, we have created biomimetic “nanosponges.” Because nanoparticles retain the same repertoire of cell membrane receptors as their host cell, they offer non-specific and all-purpose toxin decoy strategies with a broad ability to sequester and neutralize various bacterial toxins and host pro-inflammatory chemokines and cytokines to attenuate the course of infectious disease. This proof-of-concept study successfully demonstrated that intervention with nanosponges reduced the hemolytic activity of live GBS and stabilized β-H/C in a dose-dependent manner. Nanosponge treatment also decreased lung epithelial and macrophage cell death following exposure to live GBS bacteria and stabilized β-H/C, improved neutrophil killing of GBS, and diminished GBS-induced macrophage IL-1β production. Our results, therefore, suggest biomimetic nanosponges provide a titratable detoxification therapy that may provide a first-in-class treatment option for GBS infection by sequestering and inhibiting β-H/C activity.

Background: Gastroesophageal reflux disease (GERD) is a common problem in neonates, and current modalities for thickening human milk produce inconsistent outcomes. The objective of this in vitro study is to measure the viscosity effect of different thickening strategies. Methods: We thickened donor human milk (DHM) and formula using various thickeners: starch-based thickeners (SBT; Thick It, rice cereal), and gum-based thickeners (GBT; xanthan gum: Simply Thick, Thicken Up Clear; carob gum: GelMix). We also assessed formula with added starches marketed for reflux, including Similac Spit Up (SSU) and Enfamil AR (EAR). The viscosity of each sample was measured over time using a rotary viscometer. Additional variables, including acidity, temperature, and the addition of human milk fortifier, were tested. Results: Formula can be effectively thickened with all tested thickeners, but the viscosities of thickened formula increase over time. On the other hand, DHM does not effectively thicken with SBT. Autoclaving DHM inactivates digestive enzymes, thus allowing SBT to successfully thicken autoclaved DHM. GBT effectively thickened both DHM and formula but reached higher viscosities than intended based on manufacturer recommendations. Adding acid to xanthan-gum thickened DHM resulted in phase separation and formation of solid precipitant. Conclusions: Current thickening strategies of preterm infant feeding produces highly variable results in final feed viscosity. The unpredictable properties of gum-based thickeners raise questions about their safety profile. Objective measures of liquid viscosity and careful consideration of acidity and time are recommended for adequate comparisons of thickening regimens. Human milk continues to be the most challenging feed type to thicken.

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