Glucan particles (GPs) are hollow, porous 3−4 μm microspheres derived from the cell walls of Baker's yeast (Saccharomyces cerevisiae). The β-1,3-D glucan outer shell of GPs provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for efficient encapsulation of different types of payloads (DNA, siRNA, proteins, antigens, small molecules), and these payloads have been delivered in vivo by a variety of routes including oral delivery. It is known that GPs are transported across the intestinal epithelium by Peyer's patch M-cells and accumulate in a subset of CD11c+Langerin-positive dendritic cells (DC) in the subepithelial dome (SED). An increase in GP uptake in the intestinal epithelium is needed to improve our efforts to develop GPs for oral delivery of therapeutics and vaccines. In this Article, we report that polydopamine coating of GPs (PDA-GPs) increases transepithelial uptake. Synthesis of PDA-GPs was optimized to allow for encapsulation of payloads inside the hollow cavity of GPs. PDA-GPs and GP controls were orally administered to mice, and PDA-GPs showed a 42% increased uptake in SED phagocytes. PDA-GP uptake by SED phagocytes in control and M-cell-depleted mice demonstrated both M-celldependent and -independent mechanisms. In future studies, we will evaluate PDA-GPs for oral vaccine delivery and the use of PDA-functional groups for secondary surface derivatization to generate particles with ligands targeting other intestinal epithelium cell-surface receptors.

In less than a decade since its identification in 2009, the emerging fungal pathogen Candida auris has become a major public health threat due to its multidrug resistant (MDR) phenotype, high transmissibility, and high mortality. Unlike any other Candida species, C. auris has acquired high levels of resistance to an already limited arsenal of antifungals. As an emerging pathogen, there are currently a limited number of documented murine models of C. auris infection. These animal models use inoculums as high as 10 7 -10 8 cells per mouse, and the environmental and occupational exposure of working with these models has not been clearly defined. Using real-time quantitative PCR and culture, we monitored the animal holding room as well as the procedure room for up to six months while working with an intravenous model of C. auris infection. This study determined that shedding of the organism is dose-dependent, as detectable levels of C. auris were detected in the cage bedding when mice were infected with 10 7 and 10 8 cells, but not with doses of 10 5 and 10 6 cells. Autoclaving bedding in closed microisolator cages was found to be an effective way to minimize exposure to animal caretakers. We found that tissue necropsies of infected mice were also an important source of potential source exposure to C. auris. To mitigate these potential exposures, we implemented a rigorous "buddy system" workflow and a disinfection protocol that uses 10% bleach followed by 70% ethanol and can be used in any animal facility when using small animal models of C. auris infection.reported to be as high as 256 mg/L for fluconazole and > 2 mg/L for amphotericin B. (1)(2)(3)(4)(5) The Centers for Disease Control (CDC) has documented that C. auris behaves more like transmissible bacterial multidrug resistant organisms (MDROs) such as methicillin resistant Staphylococcus aureus (MRSA) than any other Candida species. (6) Of particular concern is that the unpredictable antifungal resistance profile of C. auris is also showing evidence of reduced susceptibility to the echinocandins, a third class of antifungals. ( 4) C. auris causes invasive bloodstream infections with reported mortality rates as high as 30-60% in Venezuela and India, and most recently, a reported mortality rate of up to 78% in Panama. (7)(8)(9) Although the origin of C. auris is unknown, infections with this organism have been documented on five continents in at least 18 countries, including the United States. (7,8,(10)(11)(12)(13)(14)(15)(16)(17)(18) C. auris has a predilection for the skin, making transmission and colonization from person to person quite easy (6) . C. auris has been found to be alarmingly persistent in the environment, and has been reported in hospital and nursing home settings. (19,20) A recent study at the Louis Stokes Veterans Affairs Medical Center in Cleveland, Ohio found that C. auris exhibits a greater propensity to persist for up to 7 days on surfaces than any other Candida species. Surfaces that tested positive included moist surfaces, such as hospital...